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(Received for publication, April 3, 1997, and in revised form, May 1, 1997)
From the Cardiovascular Division, Department of Medicine, Brigham
and Women's Hospital and Harvard Medical School, Boston, Massachusetts
02115
ABSTRACT In cardiac myocytes, as well as
specialized conduction and pacemaker cells, agonist binding to
muscarinic acetylcholine receptors (mAchRs) results in the
activation of several signal transduction cascades including the
endothelial isoform of nitric-oxide synthase (eNOS) expressed in these
cells. Recent evidence indicates that, as in endothelial cells, eNOS in
cardiac myocytes is localized to plasmalemma caveolae, specialized
lipid microdomains that contain caveolin-3, a muscle-specific isoform
of the scaffolding protein caveolin. In this report, using a
detergent-free method for isolation of sarcolemmal caveolae from
primary cultures of adult rat ventricular myocytes, we demonstrated
that the muscarinic cholinergic agonist carbachol promotes the
translocation of mAchR into low density gradient fractions containing
most myocyte caveolin-3 and eNOS. Following isopycnic centrifugation,
the different gradient fractions were exposed to the muscarinic
radioligand [3H]quinuclidinyl benzilate (QNB), and
binding was determined after membrane filtration or
immunoprecipitation. In a direct radioligand binding assay, we found
that [3H]QNB binding can be detected in caveolin-enriched
fractions only when cardiac myocytes have been previously exposed to
carbachol. Furthermore, most of this [3H]QNB binding can
be specifically immunoprecipitated by an antibody to the m2 mAchR,
indicating that the translocation of this receptor subtype is
responsible for the [3H]QNB binding detected in the low
density fractions. Moreover, the [3H]QNB binding could be
quantitatively immunoprecipitated from the light membrane fractions
with a caveolin-3 antibody (but not a control IgG1 antibody),
confirming that the m2 mAchR is targeted to caveolae after carbachol
treatment. Importantly, atropine, a muscarinic cholinergic antagonist,
did not induce translocation of m2 mAchR to caveolae and prevented
receptor translocation in response to the agonist carbachol.
Thus, dynamic targeting of sarcolemmal m2 mAchR to caveolae
following agonist binding may be essential to initiate specific
downstream signaling cascades in these cells.
INTRODUCTION The activation of a muscarinic acetylcholine receptor
(mAChR)1 triggers a number of signal
transduction pathways that, in the heart, may elicit both positively
and negatively inotropic and chronotropic effects (1, 2). Recent
studies have shown that, of the five mAchR subtypes identified to date,
only the m1 and m2 subtypes are expressed in adult mammalian cardiac
tissues (3, 4). According to these reports, the m2 mAchR, which is
expressed at a much higher level than the m1 mAchR, triggers the
inhibitory response while m1 receptor activation elicits, when
stimulated by higher concentrations of agonist, a compensatory
excitatory effect on heart function. Therefore, distinct downstream
signaling cascades must be involved following m1 and m2 mAchR
activation. Both m1 and m2 receptor subtypes also have been reported to
undergo translocation into specific subcompartments derived from the
plasma membrane (5-10), a characteristic of many G protein-coupled
receptors (GPR) following agonist binding. To date, two major pathways
for GPR clustering and sequestration have been reported, which involve plasma membrane modifications that lead to the formation of either clathrin-coated or non-coated vesicles (11). While the human muscarinic
cholinergic receptor Hm1 has been shown to internalize via
clathrin-coated vesicles (10), mAchR have also been shown to be
internalized through non-clathrin-coated vesicles in human fibroblasts,
although the identity of these vesicular structures has not been
defined (6).
Recently, a clathrin-independent sequestration pathway has received
attention with the characterization of a population of plasmalemmal
vesicles termed caveolae. Caveolae are small flask-shaped invaginations
of the plasma membrane characterized by high levels of cholesterol and
glycosphingolipids (12), the principal scaffolding protein of which are
the caveolins, 20-24 kDa integral membrane proteins that undergo
homo-oligomerization (13). These specialized lipid microdomains have
been shown to play a role in the compartmentation of a number of plasma
membrane-linked signal transduction pathways, including those mediated
by receptor tyrosine kinases (14, 15). In addition, a recent report by
Parton et al. (16) provides additional evidence that
coalescence and fission of caveolae may be essential for the
development of the T-tubular system that is essential for normal
intracellular calcium homeostasis and excitation-contraction coupling
in cardiac and skeletal muscle. The specific mechanisms involved in
receptor sequestration may differ among distinct cellular phenotypes.
For example, several reports have proposed the involvement of
clathrin-coated pits in the mechanism of internalization of
The recent development of antibodies directed against different
tissue-specific isoforms of caveolin has permitted a better characterization of caveolar microdomains. Using these antibodies in
immunoprecipitation experiments, we have recently shown that eNOS, the
constitutively expressed isoform of nitric-oxide synthase in cardiac
myocytes, is targeted to sarcolemmal caveolae in cardiac myocytes and
endothelial cells (19). Interestingly, reports from our laboratory and
by others have shown that the generation of nitric oxide (NO) is an
obligate intermediate step in the signal transduction cascade involved
in the m2 mAchR-mediated inhibitory responses of the heart,
particularly following In this report, we describe experiments designed to explore the
hypothesis that m2 mAchR are targeted to plasmalemmal caveolae upon
agonist stimulation in adult rat ventricular myocytes. Using a
detergent-free method for caveolae isolation followed by isopycnic centrifugation, we provide evidence that the m2 mAchR, after agonist stimulation, co-purifies with caveolin-3 and eNOS. Furthermore, we show
that the radioliganded m2 mAchR can be specifically immunoprecipitated from these caveolin-enriched fractions using antibodies directed against caveolin-3.
EXPERIMENTAL PROCEDURES Purified adult rat ventricular myocyte (ARVM)
primary cultures were plated on laminin and cultured for 24 h in a
defined medium as reported previously (19). ARVM were incubated either
with or without carbachol (100 µM, 15 min), lysed, and
fractionated on sucrose gradients; in some experiments (see "Results
and Discussion"), myocytes were preincubated in the presence of 1 µM atropine (15 min) or 5 mM acetic acid (5 min) before carbachol treatment. Before harvesting, cells were washed
extensively with ice-cold phosphate-buffered saline to ensure complete
removal of drugs. This was validated by the lack of any detectable
difference in specific [3H]quinuclidinyl benzylate (QNB)
binding levels (see below) in total lysates of ARVM, whether treated or
not with a muscarinic agonist or antagonist.
ARVM were scraped in a freshly prepared solution of 200 mM
Na2CO3 and lysed by sonication (three 5-s
bursts, minimal output power) using a Branson sonifier 450 (Branson
Ultrasonic Corp., Danbury, CT), according to a method modified from
Song et al. (26). The cell lysate was then adjusted to 45%
sucrose by addition of a sucrose stock solution prepared in MBS (25 mM Mes, pH 6.5, 150 mM NaCl) and placed at the
bottom of a 5-15-25-35% discontinuous sucrose gradient (in MBS
containing 100 mM Na2CO3) for an
overnight ultracentrifugation (150,000 g). The gradient was
fractionated in nine fractions corresponding to sucrose concentrations
5, 15, 25, 35, and 45%, and the four intermediate interfaces. Each
fraction was neutralized with HCl before further analysis.
Heat-denatured proteins were
loaded and separated on 12% SDS-polyacrylamide gels (Mini Protean II,
Bio-Rad) and transferred to a PVDF membrane (Bio-Rad). After blocking
with 5% non-fat dry milk in Tris-buffered saline with 0.1% (v/v)
Tween 20 (TBST), membranes were incubated with the specified primary
antibody (Transduction Labs) for 1 h in TBST containing 1%
non-fat dry milk. After six washes (10 min each), the membranes were
incubated for 1 h with a horseradish peroxidase-labeled goat
anti-mouse immunoglobulin secondary antibody (Jackson ImmunoResearch
Labs) at a 1:10,000 dilution in TBST containing 1% non-fat dry milk.
After five additional washes, the membranes were rinsed once in TBST,
incubated with a chemiluminescent reagent according to the manufacturer
protocols (Renaissance, NEN Life Science Products), and exposed to
x-ray film.
Mannosidase II activity was determined by
hydrolysis of
p-nitrophenyl- The
gradient fractions (buffered at pH 7.4) were adjusted to 5 mM MgCl2, 1 mM EGTA, 1 µg/ml
leupeptin, 1 µg/ml pepstatin, and 1 mM
phenylmethylsulfonyl fluoride, and aliquots of the different fractions
were incubated with 2 nM [3H]QNB (NEN Life
Science Products) at 30 °C for 60 min; nonspecific binding was
determined in the presence of 1 µM atropine. Assays were
performed in triplicate and terminated by rapid filtration on Whatman
GF/B filters or followed by an immunoprecipitation protocol (adapted
from those in Refs. 31 and 32). For these immunoprecipitation
experiments, the binding buffer also contained 1% digitonin and 0.2%
CHAPS; nonspecific [3H]QNB binding was determined by
performing all the steps of the immunoprecipitation protocol in the
presence of 1 µM atropine. After sequential incubations
of the [3H]QNB-bound receptors with an antibody directed
against the m2 mAchR (4 h, 4 °C, Chemicon) and agarose-conjugated
protein-G (1-2 h, 4 °C), immunocomplexes were precipitated by
centrifugation, washed four times with 25 mM Mes buffer
containing 1% digitonin and 0.2% CHAPS, and resuspended in 1% SDS. A
similar protocol was used for the immunoprecipitation with the
caveolin-3 antibody (Transduction Labs) except that binding and washing
buffers did not contain digitonin. The isoform specificity and lack of
cross-reactivity of the caveolin (19, 24-26) and muscarinic (32)
antibodies have been established previously. Moreover, the specificity
of the caveolin-3 immunoprecipitation was established by comparing the
[3H]QNB binding detected from immunoprecipitates
performed using a non-immune idiotype-specific purified mouse myeloma
IgG1 (Zymed). In all the experiments described here above, samples were
transferred in counting vials containing 10 ml of scintillant, and the
radioactivity was determined in a liquid scintillation counter.
RESULTS AND DISCUSSION Caveolin-enriched membranes have been historically
isolated on the basis of their insolubility in Triton due to their
specialized lipid composition (12, 33). However, it has been reported recently that the inclusion of detergent can result in the loss of
proteins normally associated with caveolae (26, 34), as well as in
apparent redistribution of mitochondrial and endoplasmic reticulum
proteins into caveolae (35). Therefore, for isolating caveolae from
cardiac myocytes, we have optimized a detergent-free purification
method based on the resistance to extraction of caveolin complexes by
sodium carbonate and on the fine disruption of cellular membrane by
sonication (18, 26). Thus, after homogenization of ARVM in a sodium
carbonate buffer, the lysate was adjusted to 45% sucrose and placed at
the bottom of a 5-15-25-35% discontinuous gradient for an overnight
ultracentrifugation. Aliquots of the different fractions collected were
separated by SDS-PAGE, transferred onto PVDF membranes, and
immunoblotted with anti-caveolin-3 or anti-eNOS antibodies. The
immunoblots presented in Fig. 1A show that
the majority of caveolin-3 and eNOS in ventricular myocytes appears in
fractions 2 and 3, which correspond to the 5-15% sucrose equilibrium
densities. This co-purification of eNOS and caveolin-3 is in agreement
with our previous data on the co-immunoprecipitation of these two
proteins from CHAPS-solubilized cardiac myocyte lysates (19) and on the
co-isolation of eNOS and caveolin-1 in endothelial cells (36).
The gradient fractions were also analyzed for their protein content as
well as for the presence of mannosidase II, as a Golgi marker (29), and
for the level of specific [3H]oubain binding (30), as a
specific marker of (Na+, K+)-ATPase, a
relatively evenly distributed enzyme at the sarcolemmal surface of
cardiac myocytes. As shown by the pattern of distribution of these
markers across the gradient (Fig. 1B), the bulk of cellular protein that equilibrates at the high sucrose density (fractions 7-9),
corresponds to Golgi and sarcolemmal membranes. The small amount of
caveolin-3 and eNOS associated with these high density fractions (Fig.
1A) is probably due to some association of both proteins
with the trans-Golgi network (37) or to incomplete cell lysis prior to
sucrose density gradient centrifugation.
We next explored the effects of
carbachol, a muscarinic cholinergic agonist, on the distribution of
mAchR using the centrifugation protocol described above, to determine
if a change in receptor subcellular localization was induced by agonist
binding. The following experiments were performed on primary cultures
of ARVM exposed to 100 µM carbachol for 15 min. After
extensive washing, myocytes were lysed and submitted to isopycnic
centrifugation on a sucrose gradient. Aliquots of the different
fractions obtained were incubated with [3H]QNB, a
muscarinic antagonist radioligand, at 30 °C for 60 min. In a first
set of experiments, membranes were directly filtered on Whatman GF/B
glass filters. As shown in Fig. 2A, in
lysates prepared from untreated myocytes, the binding of
[3H]QNB is only detected in the high-density fractions.
In contrast, following carbachol treatment, 27.4 ± 3.3% of the
[3H]QNB binding (n = 6) can be recovered
in the low-density fractions 2 and 3, which correspond to the
caveolin-enriched membranes (Fig. 1A). The rest of the
[3H]QNB binding remains concentrated in fractions 7-9
and likely represents binding to non-caveolar sarcolemmal muscarinic
receptors.
In a second series of experiments, we used a complementary approach to
explore the carbachol-induced shift in [3H]QNB binding.
The different fractions collected after isopycnic centrifugation were
immunoprecipitated using an m2 mAchR antibody, and the amount of
specific [3H]QNB binding in each immunoprecipitate was
determined. As shown in Fig. 2B, the pattern of distribution
of m2 mAchR is similar to that directly deduced from the
[3H]QNB binding to each fraction (Fig.
2A) with, however, a more accentuated shift
of [3H]QNB bound m2 mAchR toward the low density
fractions when myocytes have been exposed to carbachol. 34.6 ± 3.9% (n = 6) of the [3H]QNB binding is
now detected in the caveolar fractions 2 and 3. Importantly, when ARVM
are preincubated with 1 µM atropine before carbachol
treatment (Fig. 2C), the enrichment of the m2 mAchR in
fractions 2 and 3 is no longer observed, thereby indicating the
specificity of the agonist-mediated clustering process. Interestingly, in a previous study, Raposo et al. (6) reported that
treatment of human fibroblasts, either with a muscarinic cholinergic
agonist or with the muscarinic cholinergic antagonist atropine,
triggered the redistribution of the Hm1 mAchR into specific regions of
the plasma membrane, presumably caveolae, and that only longer
exposures with the agonist lead to the receptor endocytosis.
Furthermore, Tolbert and Lameh (10) showed, using immunofluorescence
confocal microscopy, that the Hm1 mAchR, after agonist stimulation, are internalized via clathrin-coated vesicles in HEK cells stably transfected with the epitope-tagged Hm1 receptors. Together with the
data reported here, these results suggest that the extent and the mode
of receptor compartmentation in response to agonist stimulation may be
governed by both the receptor subtype and the cell type in which it is
expressed.
In our experimental conditions, it is unlikely that clustering of the
m2 mAchR into coated pits can explain the shift in mAchR into lower
density sucrose gradients. Indeed, evidence from the literature
indicates that the equilibrium density of clathrin-coated pits is
higher than that of caveolae (38) and therefore would not match the
pattern of distribution of carbachol-stimulated muscarinic receptors
obtained in Fig. 2, A and B. Furthermore, when
myocytes are pre-incubated with 5 mM acetic acid, pH 5.0, a
treatment known to disrupt clathrin-mediated endocytosis (39), a
movement of m2 mAchR into caveolin-enriched fractions is still detected
(Fig. 2C).
To confirm the dynamic targeting
of muscarinic receptors to caveolae in cardiac myocytes, we used a
caveolin-3 antibody to immunoprecipitate caveolar membranes and
identify the m2 mAchR by radioligand binding assays. In these studies,
cardiac myocytes preincubated either with or without carbachol were
lysed and fractionated on sucrose gradients, and the fractions
corresponding to caveolae were pooled and incubated with
[3H]QNB. After subsequent incubation with either an
anti-caveolin-3 antibody or a nonspecific IgG1 antibody and
agarose-conjugated protein-G, immunocomplexes were collected by
centrifugation, and radioactivity was determined in a scintillation
counter.
As summarized in Fig. 3, in the absence of carbachol treatment, there
was no significant immunoprecipitation of [3H]QNB binding
by caveolin-3 antibodies since the level of [3H]QNB
binding was similar to that obtained when using the nonspecific IgG1
for the immunoprecipitation. In contrast, following agonist treatment,
a substantial fraction of specific [3H]QNB binding can be
immunoprecipitated by anti-caveolin-3 antibodies (Fig. 3); no change in
caveolin-3 expression was observed after carbachol treatment (not
shown). In fact, 73 ± 5% (n = 3) of the [3H]QNB binding originally present in pooled fractions 2 and 3 (determined by direct filtration on Whatman GF/B glass filters)
could be recovered after anti-caveolin-3 immunoprecipitation. Similar
experiments (not shown) performed on fractions 7-9, which correspond
to the bulk of plasma membrane (80-95% of total protein when pooled
together), did not reveal any specific [3H]QNB binding in
the caveolin-3 immunoprecipitate, in agreement with the low abundance
of caveolin-3 in these fractions (see Fig. 1A). Importantly,
in myocytes incubated with carbachol in the presence of the muscarinic
antagonist atropine, the [3H]QNB binding
immunoprecipitated by anti-caveolin-3 antibodies remained at the level
detected in a control immunoprecipitation performed with a nonspecific
IgG1. This is in agreement with the data shown in Fig. 2C in
which no significant binding was detected in the anti-m2 mAchR
immunoprecipitates from caveolar fractions of myocytes incubated with
carbachol in the presence of atropine. Taken together, these data
establish that the m2 mAchR redistributes to plasmalemmal caveolae of
cardiac myocytes following agonist binding.
The dynamic targeting of the m2 mAchR to caveolae has important
implications for muscarinic receptor biology as well as for the
regulation of eNOS activation. Although several laboratories have
reported evidence for the translocation to low density gradient fractions of the muscarinic receptors upon agonist stimulation (5-7),
there are, to our knowledge, no data in the literature that address the
specific nature of these "light membranes." The co-purification and
co-immunoprecipitation (this study, and also see Refs. 19 and 36) of
caveolin, eNOS, and the agonist-stimulated m2 mAchR in isopycnic
centrifugation fractions, which together represent less than 5% of the
total amount of protein, indicate that caveolae are the common
structural platform for these proteins. Together with immunoelectron
microscopy data showing that, in A431 cells, While numerous studies present the sequestration of G protein-coupled
receptors after agonist stimulation as a key event for initiating a
process of desensitization (for review, see Ref. 40), the data in this
manuscript support the hypothesis that, following stimulation by
agonist, cardiac m2 mAchR translocation to caveolae may be necessary to
initiate specific downstream signaling cascades. Interestingly, several
recent studies have shown that internalization of the m2 and m4 mAchR
is mediated by mechanisms distinct from the phosphorylation by the G
protein-coupled receptor kinase (GRK) family known to lead to receptor
desensitization (41, 42). The translocation of muscarinic receptors
within caveolae should allow their interaction with the heterotrimeric G protein complexes known to be concentrated within these plasmalemmal microdomains (12, 26, 28) and lead, after recruitment of co-factors and
intermediate effector proteins, to the activation of eNOS, a resident
caveolar protein in cardiac myocytes. Analysis of caveolin-enriched
fractions to identify additional signaling molecules involved in the
muscarinic cholinergic stimulation of the NO pathway in cardiac
myocytes is ongoing in our laboratory. The caveolar compartmentation
described here for the muscarinic cholinergic pathway may serve as a
paradigm for other G protein receptor-mediated signaling cascades that
are targeted to caveolae.
FOOTNOTES REFERENCES
Volume 272, Number 28,
Issue of July 11, 1997
pp. 17744-17748
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
,
-adrenergic receptors (-AR) (17), and yet a recent report
indicated that in epidermoid A431 cells, -AR are clustered within
caveolae in response to agonist stimulation (18).
-adrenergic stimulation (20-23). Caveolae
may, therefore, constitute the structural framework within which this
signaling cascade operates. Thus, the dynamic targeting of
agonist-stimulated muscarinic cholinergic receptors to caveolae in
cardiac myocytes could facilitate the activation of eNOS, which we have
shown to be quantitatively and specifically associated with caveolin-3,
the muscle-specific isoform of caveolin (19, 24-26). The
co-localization in caveolae of this
Ca2+/calmodulin-dependent NOS isoform with
proteins known to regulate Ca2+ homeostasis, including a
Ca2+-ATPase and InsP3 receptor-like proteins
(27), as well as with heterotrimeric G proteins (12, 26, 28), suggest
that these plasmalemmal microdomains may constitute a platform for the
recruitment and regulation of the signaling proteins involved in the
NO-mediated muscarinic cholinergic pathway in heart muscle.
-D-mannopyranoside (Sigma) with
volumes reduced to facilitate the assay in 96-well plates, as described
previously (29). After incubation at 37 °C for 1 h followed by
quenching with 100 mM NaOH, absorbance was measured at 405 nm using a Microplate Reader (SLT Lab Instruments).
[3H]ouabain (NEN Life Science Products) binding was
determined as described (30); nonspecific binding was estimated in the
presence of 1 mM ouabain (Sigma). Membranes were collected
on Whatman GF/B fiber filters, washed twice with chilled Tris-HCl, pH
7.4, and the radioactivity was determined in a scintillation counter.
Protein amounts, mannosidase activity and [3H]ouabain
binding are expressed as percent of total protein, of total activity,
and of total specific [3H]ouabain binding,
respectively.
Fig. 1.
Fractionation of cardiac myocytes.
A, distribution of caveolin-3 and eNOS proteins. After
isopycnic centrifugation of adult rat ventricular myocytes on sucrose
gradients as described in the text, aliquots of 1 ml-fractions were
resolved by SDS-PAGE (12.5% acrylamide), transferred onto PVDF
membranes, and immunoblotted with an anti-caveolin-3 antibody or eNOS
antibody. Fraction 1 refers to the top of the gradient. These data
represent the result of a typical fractionation experiment.
B, distribution of protein (
), plasma membrane (
), and
Golgi (
) markers along sucrose density gradient. The mannosidase II
activity and the [3H]oubain binding have been used as
specific markers of the Golgi and the plasma membrane, respectively.
Fraction 1 refers to the top of the gradient. The data represent the
results of typical fractionation procedures with individual
measurements performed in triplicate.
[View Larger Version of this Image (33K GIF file)]
Fig. 2.
Agonist-induced translocation of muscarinic
receptors in cardiac myocytes. The presence of muscarinic
receptors in each fraction is determined by the amount of specific
[3H]QNB binding detected by harvesting membranes on
Whatman glass filters (A) or by immunoprecipitation with
anti-m2 antibodies (B, C); control and carbachol (100 µM, 15 min) conditions are symbolized by open () and
closed (, , 
) symbols, respectively. In panel C,
the incubation in presence of carbachol (100 µM, 15 min)
was preceded by a 15-min incubation with atropine 1 µM
() or a 5-min incubation with 5 mM acetic acid, pH 5.0 (). For each condition, nonspecific binding was determined in the
presence of 1 µM atropine. The data are expressed as the
percent of total specific [3H]QNB binding and are
representative of those obtained in three to six experiments.
[View Larger Version of this Image (17K GIF file)]
Fig. 3.
Caveolin-immunoprecipitation of
agonist-stimulated muscarinic receptors. Low density
caveolin-enriched fractions (fractions 2 and 3, see Fig. 1) isolated
from cardiac myocytes pretreated with or without carbachol (100 µM, 15 min) were incubated with [3H]QNB at
30 °C for 30 min and immunoprecipitated using an anti-caveolin-3 or
nonspecific IgG1 antibody. Total and nonspecific [3H]QNB
binding were determined by performing immunoprecipitations in the
absence or presence of 1 µM atropine. The results
represent the specific [3H]QNB binding (± S.E.,
n = 3-5; *, p < 0.01 versus all other conditions) determined from each
immunoprecipitation and are expressed as cpm/mg of protein.
[View Larger Version of this Image (36K GIF file)]
-AR are sequestrated
within caveolae in response to agonist stimulation (18), our data
indicate that clathrin-coated pit formation can no longer be considered
as the exclusive pathway for clustering G protein-coupled receptors
within specialized plasmalemmal microdomains. The fate of caveolar
-AR and mAchR is uncertain, since it is not clear whether caveolae
pinch off from the plasma membrane and lead to early endosomes. If this is the case, it suggests that dual pathways of receptor internalization may exist in some cells.
Recipient of a fellowship from the Belgian American Educational
Foundation and of a grant from the "Patrimoine Facultaire de
l'UCL" (Belgium).
§
A Wyeth-Ayerst Established Investigator of the American Heart
Association and recipient of a Scholar Award in Experimental Therapeutics from the Burroughs-Wellcome Fund.
¶
To whom correspondence should be addressed: Cardiovascular
Div., Brigham and Women's Hospital, Harvard Medical School, 75 Francis
St., Boston, MA 02115. Tel.: 617-732-7503; Fax: 617-732-5132; E-mail:
rakelly{at}bics.bwh.harvard.edu or michel{at}calvin.bwh.harvard.edu.
1
The abbreviations used are: mAchR, muscarinic
acetylcholine receptor(s); GPR, G protein-coupled receptor; -AR,
-adrenergic receptor; eNOS, endothelial isoform of nitric-oxide
synthase; NO, nitric oxide; ARVM, adult rat ventricular myocytes; QNB,
1-quinuclidinyl benzilate; CHAPS,
3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid; Mes,
4-morpholineethanesulfonic acid; MBS, Mes-buffered saline; PVDF,
polyvinylidene difluoride; TBST, Tris-buffered saline with Tween 20;
PAGE, polyacrylamide gel electrophoresis.
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
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 P. Savi, J.-L. Zachayus, N. Delesque-Touchard, C. Labouret, C. Herve, M.-F. Uzabiaga, J.-M. Pereillo, J.-M. Culouscou, F. Bono, P. Ferrara, et al. The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts PNAS, July 18, 2006; 103(29): 11069 - 11074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Patel, B. P. Head, H. N. Petersen, I. R. Niesman, D. Huang, G. J. Gross, P. A. Insel, and D. M. Roth Protection of adult rat cardiac myocytes from ischemic cell death: role of caveolar microdomains and {delta}-opioid receptors Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H344 - H350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhao, H. H. Loh, and P. Y. Law Adenylyl Cyclase Superactivation Induced by Long-Term Treatment with Opioid Agonist Is Dependent on Receptor Localized within Lipid Rafts and Is Independent of Receptor Internalization Mol. Pharmacol., April 1, 2006; 69(4): 1421 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Martin, K. Emanuel, C. E. Sears, Y.-H. Zhang, and B. Casadei Are myocardial eNOS and nNOS involved in the {beta}-adrenergic and muscarinic regulation of inotropy? A systematic investigation Cardiovasc Res, April 1, 2006; 70(1): 97 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Fu, X. Huang, H. Zhong, R. M. Mortensen, L. G. D'Alecy, and R. R. Neubig Endogenous RGS Proteins and G{alpha} Subtypes Differentially Control Muscarinic and Adenosine-Mediated Chronotropic Effects Circ. Res., March 17, 2006; 98(5): 659 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Feron and J.-L. Balligand Caveolins and the regulation of endothelial nitric oxide synthase in the heart Cardiovasc Res, March 1, 2006; 69(4): 788 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. Head, H. H. Patel, D. M. Roth, N. C. Lai, I. R. Niesman, M. G. Farquhar, and P. A. Insel G-protein-coupled Receptor Signaling Components Localize in Both Sarcolemmal and Intracellular Caveolin-3-associated Microdomains in Adult Cardiac Myocytes J. Biol. Chem., September 2, 2005; 280(35): 31036 - 31044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Shaltout and A. A. Abdel-Rahman Mechanism of Fatty Acids Induced Suppression of Cardiovascular Reflexes in Rats J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1328 - 1337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E.J.F. Danson, Y.H. Zhang, C.E. Sears, A.R. Edwards, B. Casadei, and D.J. Paterson Disruption of inhibitory G-proteins mediates a reduction in atrial {beta}-adrenergic signaling by enhancing eNOS expression Cardiovasc Res, September 1, 2005; 67(4): 613 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Macdonald and L. J. Pike A simplified method for the preparation of detergent-free lipid rafts J. Lipid Res., May 1, 2005; 46(5): 1061 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Smith, E. B. Babiychuk, K. Noble, A. Draeger, and S. Wray Increased cholesterol decreases uterine activity: functional effects of cholesterol alteration in pregnant rat myometrium Am J Physiol Cell Physiol, May 1, 2005; 288(5): C982 - C988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-L. Wang, D. Ye, T. E. Peterson, S. Cao, V. H. Shah, Z. S. Katusic, G. C. Sieck, and H.-C. Lee Caveolae Targeting and Regulation of Large Conductance Ca2+-activated K+ Channels in Vascular Endothelial Cells J. Biol. Chem., March 25, 2005; 280(12): 11656 - 11664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Crossthwaite, T. Seebacher, N. Masada, A. Ciruela, K. Dufraux, J. E. Schultz, and D. M. F. Cooper The Cytosolic Domains of Ca2+-sensitive Adenylyl Cyclases Dictate Their Targeting to Plasma Membrane Lipid Rafts J. Biol. Chem., February 25, 2005; 280(8): 6380 - 6391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Monastyrskaya, A. Hostettler, S. Buergi, and A. Draeger The NK1 Receptor Localizes to the Plasma Membrane Microdomains, and Its Activation Is Dependent on Lipid Raft Integrity J. Biol. Chem., February 25, 2005; 280(8): 7135 - 7146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Liu, J. Abramowitz, A. Askari, and J. C. Allen Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2173 - H2182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. B. Massion, C. Dessy, F. Desjardins, M. Pelat, X. Havaux, C. Belge, P. Moulin, Y. Guiot, O. Feron, S. Janssens, et al. Cardiomyocyte-Restricted Overexpression of Endothelial Nitric Oxide Synthase (NOS3) Attenuates {beta}-Adrenergic Stimulation and Reinforces Vagal Inhibition of Cardiac Contraction Circulation, October 26, 2004; 110(17): 2666 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xue, C. M. Vines, T. Buranda, D. F. Cimino, T. A. Bennett, and E. R. Prossnitz N-Formyl Peptide Receptors Cluster in an Active Raft-associated State Prior to Phosphorylation J. Biol. Chem., October 22, 2004; 279(43): 45175 - 45184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Gonzalez, A. Nagiel, A. J. Lin, D. E. Golan, and T. Michel Small Interfering RNA-mediated Down-regulation of Caveolin-1 Differentially Modulates Signaling Pathways in Endothelial Cells J. Biol. Chem., September 24, 2004; 279(39): 40659 - 40669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Pepe, O. W.V van den Brink, E. G Lakatta, and R.-P. Xiao Cross-talk of opioid peptide receptor and {beta}-adrenergic receptor signalling in the heart Cardiovasc Res, August 15, 2004; 63(3): 414 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Odley, H. S. Hahn, R. A. Lynch, Y. Marreez, H. Osinska, J. Robbins, and G. W. Dorn II Regulation of cardiac contractility by Rab4-modulated {beta}2-adrenergic receptor recycling PNAS, May 4, 2004; 101(18): 7082 - 7087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Millar, Z.-L. Lu, A. J. Pawson, C. A. Flanagan, K. Morgan, and S. R. Maudsley Gonadotropin-Releasing Hormone Receptors Endocr. Rev., April 1, 2004; 25(2): 235 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Liang, P. K. Curran, Q. Hoang, R. T. Moreland, and P. H. Fishman Differences in endosomal targeting of human {beta}1- and {beta}2-adrenergic receptors following clathrin-mediated endocytosis J. Cell Sci., February 15, 2004; 117(5): 723 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Vallejo and C. D. Hardin Metabolic organization in vascular smooth muscle: distribution and localization of caveolin-1 and phosphofructokinase Am J Physiol Cell Physiol, January 1, 2004; 286(1): C43 - C54. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. N. Dedkova, X. Ji, Y. G. Wang, L. A. Blatter, and S. L. Lipsius Signaling Mechanisms That Mediate Nitric Oxide Production Induced by Acetylcholine Exposure and Withdrawal in Cat Atrial Myocytes Circ. Res., December 12, 2003; 93(12): 1233 - 1240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Y. Xu, S. P. Kuppusamy, J. Q. Wang, H. Li, H. Cui, T. M. Dawson, P. L. Huang, A. L. Burnett, P. Kuppusamy, and L. C. Becker Nitric Oxide Protects Cardiac Sarcolemmal Membrane Enzyme Function and Ion Active Transport against Ischemia-induced Inactivation J. Biol. Chem., October 24, 2003; 278(43): 41798 - 41803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rapacciuolo, S. Suvarna, L. Barki-Harrington, L. M. Luttrell, M. Cong, R. J. Lefkowitz, and H. A. Rockman Protein Kinase A and G Protein-coupled Receptor Kinase Phosphorylation Mediates {beta}-1 Adrenergic Receptor Endocytosis through Different Pathways J. Biol. Chem., September 12, 2003; 278(37): 35403 - 35411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.B. Massion, O. Feron, C. Dessy, and J.-L. Balligand Nitric Oxide and Cardiac Function: Ten Years After, and Continuing Circ. Res., September 5, 2003; 93(5): 388 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Pawson, S. R. Maudsley, J. Lopes, A. A. Katz, Y.-M. Sun, J. S. Davidson, and R. P. Millar Multiple Determinants for Rapid Agonist-Induced Internalization of a Nonmammalian Gonadotropin-Releasing Hormone Receptor: A Putative Palmitoylation Site and Threonine Doublet within the Carboxyl-Terminal Tail Are Critical Endocrinology, September 1, 2003; 144(9): 3860 - 3871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Navratil, S. P. Bliss, K. A. Berghorn, J. M. Haughian, T. A. Farmerie, J. K. Graham, C. M. Clay, and M. S. Roberson Constitutive Localization of the Gonadotropin-releasing Hormone (GnRH) Receptor to Low Density Membrane Microdomains Is Necessary for GnRH Signaling to ERK J. Biol. Chem., August 22, 2003; 278(34): 31593 - 31602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kawamura, S. Miyamoto, and J. H. Brown Initiation and Transduction of Stretch-induced RhoA and Rac1 Activation through Caveolae: CYTOSKELETAL REGULATION OF ERK TRANSLOCATION J. Biol. Chem., August 15, 2003; 278(33): 31111 - 31117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Kifor, I. Kifor, F. D. Moore Jr., R. R. Butters Jr., and E. M. Brown m-Calpain Colocalizes with the Calcium-sensing Receptor (CaR) in Caveolae in Parathyroid Cells and Participates in Degradation of the CaR J. Biol. Chem., August 15, 2003; 278(33): 31167 - 31176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Liu, K. Mohammadi, B. Aynafshar, H. Wang, D. Li, J. Liu, A. V. Ivanov, Z. Xie, and A. Askari Role of caveolae in signal-transducing function of cardiac Na+/K+-ATPase Am J Physiol Cell Physiol, June 1, 2003; 284(6): C1550 - C1560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Pike Lipid rafts: bringing order to chaos J. Lipid Res., April 1, 2003; 44(4): 655 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Woodman, D. S. Park, A. W. Cohen, M. W.-C. Cheung, M. Chandra, J. Shirani, B. Tang, L. A. Jelicks, R. N. Kitsis, G. J. Christ, et al. Caveolin-3 Knock-out Mice Develop a Progressive Cardiomyopathy and Show Hyperactivation of the p42/44 MAPK Cascade J. Biol. Chem., October 4, 2002; 277(41): 38988 - 38997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Razani, S. E. Woodman, and M. P. Lisanti Caveolae: From Cell Biology to Animal Physiology Pharmacol. Rev., September 1, 2002; 54(3): 431 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Martinac and O. P. Hamill Gramicidin A channels switch between stretch activation and stretch inactivation depending on bilayer thickness PNAS, April 2, 2002; 99(7): 4308 - 4312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Yarbrough, T. Lu, H.-C. Lee, and E. F. Shibata Localization of Cardiac Sodium Channels in Caveolin-Rich Membrane Domains: Regulation of Sodium Current Amplitude Circ. Res., March 8, 2002; 90(4): 443 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Smith, C. Gu, K. A. Fagan, B. Hu, and D. M. F. Cooper Residence of Adenylyl Cyclase Type 8 in Caveolae Is Necessary but Not Sufficient for Regulation by Capacitative Ca2+ Entry J. Biol. Chem., February 15, 2002; 277(8): 6025 - 6031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Isshiki, J. Ando, K. Yamamoto, T. Fujita, Y. Ying, and R. G. W. Anderson Sites of Ca2+ wave initiation move with caveolae to the trailing edge of migrating cells J. Cell Sci., January 2, 2002; 115(3): 475 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.-P. Xiao {beta}-Adrenergic Signaling in the Heart: Dual Coupling of the {beta}2-Adrenergic Receptor to Gs and Gi Proteins Sci. Signal., October 16, 2001; 2001(104): re15 - re15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Nilius and G. Droogmans Ion Channels and Their Functional Role in Vascular Endothelium Physiol Rev, October 1, 2001; 81(4): 1415 - 1459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Razani and M. P. Lisanti Two distinct caveolin-1 domains mediate the functional interaction of caveolin-1 with protein kinase A Am J Physiol Cell Physiol, October 1, 2001; 281(4): C1241 - C1250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. M. Nascimento, L. Salle, J. Hoebeke, J. Argibay, and N. Peineau cGMP-mediated inhibition of cardiac L-type Ca2+ current by a monoclonal antibody against the M2 ACh receptor Am J Physiol Cell Physiol, October 1, 2001; 281(4): C1251 - C1258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. W. Tawfeek, J. Che, F. Qian, and A. B. Abou-Samra Parathyroid hormone receptor internalization is independent of protein kinase A and phospholipase C activation Am J Physiol Endocrinol Metab, September 1, 2001; 281(3): E545 - E557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Muller, C. Jung, S. Wied, S. Welte, H. Jordan, and W. Frick Redistribution of Glycolipid Raft Domain Components Induces Insulin-Mimetic Signaling in Rat Adipocytes Mol. Cell. Biol., July 15, 2001; 21(14): 4553 - 4567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ginés, F. Ciruela, J. Burgueño, V. Casadó, Enric. I. Canela, J. Mallol, C. Lluís, and R. Franco Involvement of Caveolin in Ligand-Induced Recruitment and Internalization of A1 Adenosine Receptor and Adenosine Deaminase in an Epithelial Cell Line Mol. Pharmacol., April 16, 2001; 59(5): 1314 - 1323. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Govers and T. J. Rabelink Cellular regulation of endothelial nitric oxide synthase Am J Physiol Renal Physiol, February 1, 2001; 280(2): F193 - F206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Roseberry and M. Hosey Internalization of the M2 muscarinic acetylcholine receptor proceeds through an atypical pathway in HEK293 cells that is independent of clathrin and caveolae J. Cell Sci., January 2, 2001; 114(4): 739 - 746. [Abstract] [PDF]
|
|
|
|
|
|
K. E Loke, E. J Messina, E. G Shesely, G. Kaley, and T. H Hintze Potential role of eNOS in the therapeutic control of myocardial oxygen consumption by ACE inhibitors and amlodipine Cardiovasc Res, January 1, 2001; 49(1): 86 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Rebecchi and S. N. Pentyala Structure, Function, and Control of Phosphoinositide-Specific Phospholipase C Physiol Rev, October 1, 2000; 80(4): 1291 - 1335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Ostrom, S. R. Post, and P. A. Insel Stoichiometry and Compartmentation in G Protein-Coupled Receptor Signaling: Implications for Therapeutic Interventions Involving Gs J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 407 - 412. [Abstract] [Full Text]
|
|
|
|
|
|
J. M. Hare, R. A. Lofthouse, G. J. Juang, L. Colman, K. M. Ricker, B. Kim, H. Senzaki, S. Cao, R. S. Tunin, and D. A. Kass Contribution of Caveolin Protein Abundance to Augmented Nitric Oxide Signaling in Conscious Dogs With Pacing-Induced Heart Failure Circ. Res., May 26, 2000; 86(10): 1085 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Ostrom, J. D. Violin, S. Coleman, and P. A. Insel Selective Enhancement of beta -Adrenergic Receptor Signaling by Overexpression of Adenylyl Cyclase Type 6: Colocalization of Receptor and Adenylyl Cyclase in Caveolae of Cardiac Myocytes Mol. Pharmacol., May 1, 2000; 57(5): 1075 - 1079. [Abstract] [Full Text]
|
|
|
|
|
|
T. P. Lockwich, X. Liu, B. B. Singh, J. Jadlowiec, S. Weiland, and I. S. Ambudkar Assembly of Trp1 in a Signaling Complex Associated with Caveolin-Scaffolding Lipid Raft Domains J. Biol. Chem., April 14, 2000; 275(16): 11934 - 11942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-W. Dong, C. Tang, and M.-S. Liu Biphasic redistribution of muscarinic receptor and the altered receptor phosphorylation and gene transcription are underlying mechanisms in the rat heart during sepsis Cardiovasc Res, March 1, 2000; 45(4): 925 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Okamoto, H. Ninomiya, S. Miwa, and T. Masaki Cholesterol Oxidation Switches the Internalization Pathway of Endothelin Receptor Type A from Caveolae to Clathrin-coated Pits in Chinese Hamster Ovary Cells J. Biol. Chem., February 25, 2000; 275(9): 6439 - 6446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Lasley, P. Narayan, A. Uittenbogaard, and E. J. Smart Activated Cardiac Adenosine A1 Receptors Translocate Out of Caveolae J. Biol. Chem., February 11, 2000; 275(6): 4417 - 4421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Y. Vollmer, P. Alix, A. Chollet, K. Takeda, and J.-L. Galzi Subcellular Compartmentalization of Activation and Desensitization of Responses Mediated by NK2 Neurokinin Receptors J. Biol. Chem., December 31, 1999; 274(53): 37915 - 37922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Blair, P. W. Shaul, I. S. Yuhanna, P. A. Conrad, and E. J. Smart Oxidized Low Density Lipoprotein Displaces Endothelial Nitric-oxide Synthase (eNOS) from Plasmalemmal Caveolae and Impairs eNOS Activation J. Biol. Chem., November 5, 1999; 274(45): 32512 - 32519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Razani, C. S. Rubin, and M. P. Lisanti Regulation of cAMP-mediated Signal Transduction via Interaction of Caveolins with the Catalytic Subunit of Protein Kinase A J. Biol. Chem., September 10, 1999; 274(37): 26353 - 26360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Schwencke, M. Yamamoto, S. Okumura, Y. Toya, S.-J. Kim, and Y. Ishikawa Compartmentation of Cyclic Adenosine 3',5'-Monophosphate Signaling in Caveolae Mol. Endocrinol., July 1, 1999; 13(7): 1061 - 1070. [Abstract] [Full Text]
|
|
|
|
|
|
Y.-Y. Zhao, O. Feron, C. Dessy, X. Han, M. A. Marchionni, and R. A. Kelly Neuregulin Signaling in the Heart : Dynamic Targeting of erbB4 to Caveolar Microdomains in Cardiac Myocytes Circ. Res., June 25, 1999; 84(12): 1380 - 1387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Ostrom and P. A. Insel Caveolar Microdomains of the Sarcolemma : Compartmentation of Signaling Molecules Comes of Age Circ. Res., May 14, 1999; 84(9): 1110 - 1112. [Full Text] [PDF]
|
|
|
|
|
|
K. E. Loke, P. I. McConnell, J. M. Tuzman, E. G. Shesely, C. J. Smith, C. J. Stackpole, C. I. Thompson, G. Kaley, M. S. Wolin, and T. H. Hintze Endogenous Endothelial Nitric Oxide Synthase–Derived Nitric Oxide Is a Physiological Regulator of Myocardial Oxygen Consumption Circ. Res., April 16, 1999; 84(7): 840 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Carman, M. P. Lisanti, and J. L. Benovic Regulation of G Protein-coupled Receptor Kinases by Caveolin J. Biol. Chem., March 26, 1999; 274(13): 8858 - 8864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Goetz, H. S. Thatte, P. Prabhakar, M. R. Cho, T. Michel, and D. E. Golan Estradiol induces the calcium-dependent translocation of endothelial nitric oxide synthase PNAS, March 16, 1999; 96(6): 2788 - 2793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Galbiati, D. Volonte, D. Meani, G. Milligan, D. M. Lublin, M. P. Lisanti, and M. Parenti The Dually Acylated NH2-terminal Domain of Gi1alpha Is Sufficient to Target a Green Fluorescent Protein Reporter to Caveolin-enriched Plasma Membrane Domains. PALMITOYLATION OF CAVEOLIN-1 IS REQUIRED FOR THE RECOGNITION OF DUALLY ACYLATED G-PROTEIN alpha SUBUNITS IN VIVO J. Biol. Chem., February 26, 1999; 274(9): 5843 - 5850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Ratovitski, M. R. Alam, R. A. Quick, A. McMillan, C. Bao, C. Kozlovsky, T. A. Hand, R. C. Johnson, R. E. Mains, B. A. Eipper, et al. Kalirin Inhibition of Inducible Nitric-oxide Synthase J. Biol. Chem., January 8, 1999; 274(2): 993 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Orsini and J. L. Benovic Characterization of Dominant Negative Arrestins That Inhibit beta 2-Adrenergic Receptor Internalization by Distinct Mechanisms J. Biol. Chem., December 18, 1998; 273(51): 34616 - 34622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Feron, C. Dessy, D. J. Opel, M. A. Arstall, R. A. Kelly, and T. Michel Modulation of the Endothelial Nitric-oxide Synthase-Caveolin Interaction in Cardiac Myocytes. IMPLICATIONS FOR THE AUTONOMIC REGULATION OF HEART RATE J. Biol. Chem., November 13, 1998; 273(46): 30249 - 30254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Shaul and R. G. W. Anderson Role of plasmalemmal caveolae in signal transduction Am J Physiol Lung Cell Mol Physiol, November 1, 1998; 275(5): L843 - L851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamamoto, Y. Toya, C. Schwencke, M. P. Lisanti, M. G. Myers Jr., and Y. Ishikawa Caveolin Is an Activator of Insulin Receptor Signaling J. Biol. Chem., October 9, 1998; 273(41): 26962 - 26968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Polyak, S. H. Tailor, and J. P. Deans Identification of a Cytoplasmic Region of CD20 Required for Its Redistribution to a Detergent-Insoluble Membrane Compartment J. Immunol., October 1, 1998; 161(7): 3242 - 3248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ishizaka, K. K. Griendling, B. Lassegue, and R. W. Alexander Angiotensin II Type 1 Receptor : Relationship With Caveolae and Caveolin After Initial Agonist Stimulation Hypertension, September 1, 1998; 32(3): 459 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Drmota, J. Novotny, G.-D. Kim, K. A. Eidne, G. Milligan, and P. Svoboda Agonist-induced Internalization of the G Protein G11alpha and Thyrotropin-releasing Hormone Receptors Proceed on Different Time Scales J. Biol. Chem., August 21, 1998; 273(34): 21699 - 21707. [Abstract] [Full Text] [PDF]
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O. Kifor, R. Diaz, R. Butters, I. Kifor, and E. M. Brown The Calcium-sensing Receptor Is Localized in Caveolin-rich Plasma Membrane Domains of Bovine Parathyroid Cells J. Biol. Chem., August 21, 1998; 273(34): 21708 - 21713. [Abstract] [Full Text] [PDF]
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O. Vogler, G. S. Bogatkewitsch, C. Wriske, P. Krummenerl, K. H. Jakobs, and C. J. van Koppen Receptor Subtype-specific Regulation of Muscarinic Acetylcholine Receptor Sequestration by Dynamin. DISTINCT SEQUESTRATION OF m2 RECEPTORS J. Biol. Chem., May 15, 1998; 273(20): 12155 - 12160. [Abstract] [Full Text] [PDF]
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T. Ikezu, B. D. Trapp, K. S. Song, A. Schlegel, M. P. Lisanti, and T. Okamoto Caveolae, Plasma Membrane Microdomains for alpha -Secretase-mediated Processing of the Amyloid Precursor Protein J. Biol. Chem., April 24, 1998; 273(17): 10485 - 10495. [Abstract] [Full Text] [PDF]
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T. Okamoto, A. Schlegel, P. E. Scherer, and M. P. Lisanti Caveolins, a Family of Scaffolding Proteins for Organizing "Preassembled Signaling Complexes" at the Plasma Membrane J. Biol. Chem., March 6, 1998; 273(10): 5419 - 5422. [Full Text] [PDF]
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H. Tsuga, K. Kameyama, T. Haga, T. Honma, J. Lameh, and W. Sadee Internalization and Down-regulation of Human Muscarinic Acetylcholine Receptor m2 Subtypes. ROLE OF THIRD INTRACELLULAR m2 LOOP AND G PROTEIN-COUPLED RECEPTOR KINASE 2 J. Biol. Chem., February 27, 1998; 273(9): 5323 - 5330. [Abstract] [Full Text] [PDF]
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O. Feron, F. Saldana, J. B. Michel, and T. Michel The Endothelial Nitric-oxide Synthase-Caveolin Regulatory Cycle J. Biol. Chem., February 6, 1998; 273(6): 3125 - 3128. [Abstract] [Full Text] [PDF]
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C. Huang, J. R. Hepler, L. T. Chen, A. G. Gilman, R. G.W. Anderson, and S. M. Mumby Organization of G Proteins and Adenylyl Cyclase at the Plasma Membrane Mol. Biol. Cell, December 1, 1997; 8(12): 2365 - 2378. [Abstract] [Full Text]
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R. Pals-Rylaarsdam, V. V. Gurevich, K. B. Lee, J. A. Ptasienski, J. L. Benovic, and M. M. Hosey Internalization of the m2 Muscarinic Acetylcholine Receptor. ARRESTIN-INDEPENDENT AND -DEPENDENT PATHWAYS J. Biol. Chem., September 19, 1997; 272(38): 23682 - 23689. [Abstract] [Full Text] [PDF]
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K. A. Fagan, K. E. Smith, and D. M. F. Cooper Regulation of the Ca2+-inhibitable Adenylyl Cyclase Type VI by Capacitative Ca2+ Entry Requires Localization in Cholesterol-rich Domains J. Biol. Chem., August 18, 2000; 275(34): 26530 - 26537. [Abstract] [Full Text] [PDF]
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K. S. Murthy and G. M. Makhlouf Heterologous Desensitization Mediated by G Protein-specific Binding to Caveolin J. Biol. Chem., September 22, 2000; 275(39): 30211 - 30219. [Abstract] [Full Text] [PDF]
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M. L. Schlador, R. D. Grubbs, and N. M. Nathanson Multiple Topological Domains Mediate Subtype-specific Internalization of the M2 Muscarinic Acetylcholine Receptor J. Biol. Chem., July 21, 2000; 275(30): 23295 - 23302. [Abstract] [Full Text] [PDF]
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J. Igarashi and T. Michel Agonist-modulated Targeting of the EDG-1 Receptor to Plasmalemmal Caveolae. eNOS ACTIVATION BY SPHINGOSINE 1-PHOSPHATE AND THE ROLE OF CAVEOLIN-1 IN SPHINGOLIPID SIGNAL TRANSDUCTION J. Biol. Chem., October 6, 2000; 275(41): 32363 - 32370. [Abstract] [Full Text] [PDF]
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V. O. Rybin, X. Xu, M. P. Lisanti, and S. F. Steinberg Differential Targeting of beta -Adrenergic Receptor Subtypes and Adenylyl Cyclase to Cardiomyocyte Caveolae. A MECHANISM TO FUNCTIONALLY REGULATE THE cAMP SIGNALING PATHWAY J. Biol. Chem., December 22, 2000; 275(52): 41447 - 41457. [Abstract] [Full Text] [PDF]
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B. Razani, X. L. Zhang, M. Bitzer, G. von Gersdorff, E. P. Bottinger, and M. P. Lisanti Caveolin-1 Regulates Transforming Growth Factor (TGF)-beta /SMAD Signaling through an Interaction with the TGF-beta Type I Receptor J. Biol. Chem., February 23, 2001; 276(9): 6727 - 6738. [Abstract] [Full Text] [PDF]
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Z. Shui, I. A. Khan, T. Haga, J. L. Benovic, and M. R. Boyett Control of the Cardiac Muscarinic K+ Channel by beta -Arrestin 2 J. Biol. Chem., April 6, 2001; 276(15): 11691 - 11697. [Abstract] [Full Text] [PDF]
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J. C. Zwaagstra, M. El-Alfy, and M. D. O'Connor-McCourt Transforming Growth Factor (TGF)-beta 1 Internalization. MODULATION BY LIGAND INTERACTION WITH TGF-beta RECEPTORS TYPES I AND II AND A MECHANISM THAT IS DISTINCT FROM CLATHRIN-MEDIATED ENDOCYTOSIS J. Biol. Chem., July 13, 2001; 276(29): 27237 - 27245. [Abstract] [Full Text] [PDF]
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B. Martinac and O. P. Hamill Gramicidin A channels switch between stretch activation and stretch inactivation depending on bilayer thickness PNAS, April 2, 2002; 99(7): 4308 - 4312. [Abstract] [Full Text] [PDF]
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