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(Received for publication, November 21, 1995; and in revised form, January
24, 1996) From the
Adducin is a membrane skeleton protein originally described in
human erythrocytes that promotes the binding of spectrin to actin and
also binds directly to actin and bundles actin filaments. Adducin is
associated with regions of cell-cell contact in nonerythroid cells,
where it is believed to play a role in regulating the assembly of the
spectrin-actin membrane skeleton. In this study we demonstrate a novel
function for adducin; it completely blocks elongation and
depolymerization at the barbed (fast growing) ends of actin filaments,
thus functioning as a barbed end capping protein (K Precise control of actin filament length is an important
functional consideration in a number of tissues including striated
muscle (1) and the erythrocyte membrane skeleton(2) .
These two examples are similar with respect to the uniform lengths of
the filament population, although the actual lengths themselves are
different, 1 µm in skeletal muscle (3) and 33-37 nm
in erythrocytes (4, 5, 6) . These uniform
length distributions suggest strict regulation of actin filament growth
because pure actin filaments polymerize to an exponential length
distribution at steady state in vitro(7) . In muscle,
control of actin filament growth is achieved by capping the fast
growing (barbed) ends with capZ (8, 9) and by capping
the slow growing (pointed) ends with
tropomodulin(10, 11, 12) . In erythrocytes,
tropomodulin caps the pointed ends of the short actin
filaments(11, 13, 14) , but a barbed end
capping protein has not yet been identified. A conserved mechanism
of actin filament length regulation between striated muscle and
erythrocytes would require a barbed end capping protein to be
identified in erythrocytes. There are five known actin binding proteins
that are associated with the short erythrocyte actin filaments:
spectrin, band 4.1, tropomyosin, tropomodulin, band 4.9, and adducin.
Most of these proteins can be ruled out because they bind along the
sides of actin filaments and have been shown directly not to block
actin polymerization from the barbed filament ends (for reviews see (15, 16, 17) ). However, several observations
raised the possibility that adducin, which was initially characterized
as a calmodulin-binding protein(18) , might be a candidate for
a novel erythrocyte barbed end capping protein. Adducin is associated
in stoichiometric amounts with the short erythrocyte actin filaments
(one In this study, we show
that whole adducin blocks elongation and depolymerization from the fast
growing (barbed) ends of actin filaments. In contrast, neither the
isolated head or tail domains have barbed end capping activity on their
own. We further demonstrate that unlike other barbed end capping
proteins, the capping activity of adducin is down-regulated by
calmodulin in the presence of calcium. Sequencing of adducin cDNAs from
erythrocytes and other tissues has demonstrated that adducins are a
unique family of proteins associated with the spectrin-based membrane
skeleton in erythroid and nonerythroid cells (for a review see (16) ). The combination of adducin's
calcium/calmodulin-regulated barbed end capping, actin bundling, and
enhancement of spectrin-actin binding activities indicates that
adducins represent a new type of regulated actin filament binding and
barbed end capping protein.
Figure 1:
Effect of adducin on
the rate of actin polymerization from the barbed ends of spectrin-actin
seeds. A, raw data. Elongation was initiated by the addition
of spectrin-actin seeds and salts to a 5 µM G-actin
solution (5% pyrenyl-actin) containing increasing concentrations of
adducin as indicated. B, percentage of inhibition of
elongation (percent capping) plotted against increasing adducin
concentrations. (The polymerization rate is calculated as a percentage
of the initial rate of polymerization in the absence of adducin and is
inversely proportional to capping.) The concentration of adducin
required to produce 50% inhibition of polymerization (100 nM)
was taken as a measure of the K
Not only can adducin completely inhibit elongation from the
barbed ends of actin filaments, but saturating amounts of adducin (700
nM) also greatly reduce the depolymerization rate of F-actin
that has been diluted below its critical concentration (Fig. 2).
This effect is primarily due to inhibition of depolymerization from the
barbed end because under the conditions of our assays the higher off
rate of the barbed ends dominates the depolymerization kinetics; for
example, even complete inhibition of depolymerization at the pointed
end in these assays would have been expected to lead to only about a
10% reduction in the rate of depolymerization(35) .
Furthermore, we observe a similar reduction in the initial rate of
actin depolymerization in the presence of saturating amounts (30
nM) of nonmuscle capping protein isolated from erythrocytes (Fig. 2), a known barbed end capping protein (30) .
Figure 2:
Effect of adducin on the rate of actin
depolymerization. Depolymerization of pyrene-labeled F-actin was
initiated by dilution of a 20 µM stock to a final
concentration of 1 µM into buffer A with or without
adducin or nonmuscle capping protein as indicated. All measurements
utilized a single actin stock to maintain a constant filament number in
the assay. Final concentrations in the assay of intact adducin were 700
nM, and that of nonmuscle capping protein was 30 nM.
Under the low salt conditions used in this assay, the final actin
concentration after dilution (1 µM) is less than the actin
critical concentration under these conditions (
Complete capping of barbed filament
ends by previously described barbed end capping proteins results in an
increase of the actin monomer concentration at steady state with the
filaments, reflecting the higher critical concentration for the pointed
ends(35, 36) . Fig. 3A shows that
saturating concentrations of nonmuscle capping protein isolated from
erythrocytes resulted in about a 3-fold increase in the amount of actin
monomer remaining in the supernatant at steady state from 0.4 to 1.3
µM. In contrast, increasing concentrations of adducin
(from 100 to 700 nM) led to a considerably smaller increase in
the amount of actin monomer in the supernatant from 0.3 to 0.6
µM (Fig. 3B). This result suggests that
adducin may reduce the critical concentration at the pointed end of the
filament in addition to blocking monomer addition and loss at the
barbed filament end. This interpretation is consistent with the
observation that adducin reduces the rate of depolymerization while
increasing the rate of elongation at the pointed filament end (data not
shown). This may be a consequence of adducin reducing the actin monomer
off rate for the pointed filament end by its binding along the sides of
actin filaments. Finally, the observation that increasing amounts of
adducin do not lead to continuously increasing amounts of
nonpolymerizable actin also demonstrates that the effects of adducin on
polymerization kinetics at the barbed filament end are not solely due
to monomer sequestration.
Figure 3:
The effect of increasing concentrations of
nonmuscle capping protein (A) or adducin (B) on actin
critical concentration. The extent of actin polymerization was
determined after a 24-h incubation by centrifugation followed by
SDS-polyacrylamide gel electrophoresis of supernatants and pellets as
described under ``Experimental Procedures.'' The amount of
actin remaining in the supernatant was taken to be the actin monomer
concentration (actin critical concentration) and plotted versus the concentration of nonmuscle capping protein and adducin using
the same y axis to facilitate comparison. The actin critical
concentration in the absence of adducin or capping protein varied from
about 0.3-0.4 µM (this experiment) down to about
0.05 µM in other experiments; however, the relative
increases in the actin critical concentration in the presence of
adducin or nonmuscle capping protein were similar in all
experiments.
In an effort to determine whether the
actin filament capping activity of adducin could be localized to either
the NH
Figure 4:
Effect of calmodulin on the ability of
adducin to inhibit actin polymerization (A) and
depolymerization (B) in the presence of calcium. A, percentage
of capping calculated as described in the legend to Fig. 1B plotted against increasing concentrations of calmodulin. The
ability of 200 nM adducin to inhibit polymerization from
spectrin-actin seeds was tested as described above except with the
inclusion of increasing concentrations of calmodulin as indicated. The
standard assay conditions contained 0.2 mM CaCl
Using both a nucleated actin polymerization assay (8) and an F-actin depolymerization assay, we have shown that
adducin caps the barbed ends of actin filaments with a K Calmodulin has been
demonstrated to regulate the mechanical properties of the erythrocyte
membrane in the presence of calcium(40) . The inhibitory effect
of calcium/calmodulin on the ability of adducin to cap the barbed ends
of actin filaments suggests that the effect of calmodulin on membrane
mechanics may be partly mediated via changes in actin filament
polymerization. Calcium/calmodulin also inhibits adducin binding to
F-actin and to spectrin-actin complexes(19, 20) , as
well as inhibiting spectrin-protein 4.1 cross-linking of actin
filaments(41, 42) . These observations emphasize that
calmodulin is likely to regulate membrane mechanical properties via
multiple effects on membrane skeleton organization. The capping
affinity of adducin is considerably lower than has been described for
other barbed end capping proteins (e.g. gelsolin = 1
pM; capping protein = 1 nM; for reviews see (9) and (36) ) and is similar to the affinity of
adducin for binding to the sides of actin filaments and bundling them (K The actin-binding sequence
homology in the NH Based on these considerations, we propose that the barbed end
capping activity of the NH
Figure 5:
A schematic model for actin capping by
adducin. The barbed end of an erythrocyte actin filament is shown with
six associated spectrin molecules(4, 6) . For clarity
only the NH
The actin capping properties
of adducin suggest that adducin could provide a link between membranes
and the barbed ends of spectrin-associated actin filaments. In
erythrocytes, adducin has been shown to bind directly to
stomatin(52) , a membrane protein that is associated with ion
channels and has been genetically linked to hereditary
stomatocytosis(2) . In nonerythroid cells, adducin is
associated with the spectrin-based membrane skeleton at cell-cell
contact sites on the lateral borders of the plasma membrane of
epithelial cells(53) . Protein kinase C phosphorylation of
adducin in cultured epithelial cells induces redistribution of adducin
away from cell-cell contact sites(53) . Functional linkage of
adducin's barbed end capping activity to the filament side
binding activity of the tails may imply that phosphorylation of tails
by protein kinase C (23) could also regulate adducin's
capping function, as we have demonstrated here for calcium/calmodulin.
It is tempting to speculate that adducin could be a regulatory target
for signal transduction pathways that lead to remodeling of the actin
cytoskeleton at cell-cell contact sites.
Volume 271,
Number 14,
Issue of April 5, 1996 pp. 7986-7991
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
CALCIUM/CALMODULIN-REGULATED CAPPING OF THE BARBED ENDS OF ACTIN
FILAMENTS (*)
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
FOOTNOTES
ACKNOWLEDGEMENTS
REFERENCES
100 nM). This barbed end capping activity requires
the intact adducin molecule and is not provided by the
NH
-terminal globular head domains alone nor by the
COOH-terminal extended tail domains, which were previously shown to
contain the spectrin-actin binding, calmodulin binding, and
phosphorylation sites. A novel difference between adducin and other
previously described capping proteins is that it is down-regulated by
calmodulin in the presence of calcium. The association of
stoichiometric amounts of adducin with the short erythrocyte actin
filaments in the membrane skeleton indicates that adducin could be the
functional barbed end capper in erythrocytes and play a role in
restricting actin filament length. Our experiments also suggest novel
possibilities for calcium regulation of actin filament assembly by
adducin in erythrocytes and at cell-cell contact sites in nonerythroid
cells.
,
heterodimer per filament) (18) and has been
shown to bind to spectrin-actin complexes and promote spectrin binding
to actin (K
= 80
nM)(19, 20) , as well as to bind directly to
F-actin (K = 280 nM)
and to bundle actin filaments(20, 21) . Curiously,
although the 39-kDa NH-terminal globular ``head''
domains of both and adducin contain a region of sequence
homology to the actin-binding domain of the -actinin family of
actin binding proteins(22) , the isolated head domains of
either or adducin do not appear to bind F-actin or
spectrin-actin complexes in cosedimentation assays (23) .
Indeed, the 33-kDa COOH-terminal extended tail domains of both the
and adducin subunits were recently shown to be sufficient
for binding to spectrin-actin complexes and for recruitment of
additional spectrin molecules(24) . Thus, the functional
significance of the actin binding sequence homology in the head domain
of adducin remained an open question and suggested that adducin might
have additional actin-binding properties.
Purification of Proteins
Actin was purified from
rabbit skeletal muscle acetone powder (25) and subsequently gel
filtered on Superose 6 to remove actin nuclei and minor contaminants.
Pyrene-labeled actin was prepared by the method of Kouyama and Mihashi (26) with the modifications of Weber et
al.(27) ; labeled and unlabeled actin was stored on ice in
buffer A (see below) and used within 1 week. Human erythrocyte adducin
was prepared from the low salt extract of human erythrocyte ghosts by
the method of Bennett (28) as modified by Hughes and Bennett (24) and stored at -80 °C in storage buffer (10%
sucrose, 10 mM sodium phosphate, 0.05% Tween 20, 1 mM sodium azide, 1 mM EDTA, and 1 mM dithiothreitol). Calmodulin was purified from bovine brain as
described(29) . Nonmuscle capping protein (30) was
purified from erythrocyte cytosol. (
)The adducin tail
domains were expressed using the bacterial expression vector pGEMEX and
purified as described in Hughes and Bennett(24) . The adducin
head domain was purified after digestion of human erythrocyte adducin
with trypsin(23) .Actin Polymerization Assays
Buffer A (2 mM Tris-HCl, 0.2 mM NaATP, 0.5 mM 2-mercaptoethanol, 0.2 mM CaCl, 0.005% sodium
azide, final pH = 8.0 at 25 °C) was used in all assays. In
all pyrene fluorescence experiments the amount of labeled actin was 5%
to prevent internal quenching of the probe. The assay used to
quantitate inhibition of actin polymerization at the barbed ends
utilized the method of Casella et al. (8) in which
polymerization was seeded using a crude low ionic strength extract of
erythrocyte membranes containing spectrin-actin oligomeric
complexes(8, 31) . Briefly, 5 µM G-actin
was primed for rapid polymerization by addition of Mg
to 0.2 mM and incubated for 5 min. Next, all other
components of the assays were added (e.g. adducin at the
concentrations indicated in the figures, 50 µg/ml spectrin-actin
complexes), and actin polymerization was initiated by increasing the
KCl concentration to 1 mM and the MgCl concentration to 0.4 mM (final). Actin polymerization
was followed by monitoring the increased pyrene fluorescence of labeled
F-actin (excitation at 365 nm and emission of 407 nm) using a SLM8000
spectrofluorimeter. The fluorescence data were saved to a computer disc
for subsequent analysis. Actin depolymerization was initiated by
dilution of a 20 µM stock of F-actin (polymerized
overnight at 4 °C) to a final concentration of 1 µM in
buffer A alone or buffer A containing adducin or capping protein; actin
depolymerization was indicated by a decrease in pyrene fluorescence.
The sample temperature was maintained at a constant 25 °C for all
actin polymerization experiments and at 37 °C for actin
depolymerization experiments using a circulating water bath. Initial
rates of polymerization and depolymerization were determined using the
linear regression analysis feature of the graphics program Cricket
Graph running on a Macintosh.Actin Critical Concentration Assay
5 µM G-actin in buffer A was mixed with increasing amounts of adducin
or capping protein and polymerized by the addition of KCl and
Mg to 100 and 2 mM, respectively. After 24 h
of incubation at 4 °C, F-actin was collected by sedimentation for 1
h at 435,000 
g in a Beckman TL100 rotor at 4 °C.
(The sensitivity of adducin to proteolytic degradation during prolonged
incubations at room temperature made it necessary to do this experiment
at 4 °C.) The supernatant was carefully removed, and the G-actin
remaining in the supernatant was precipitated by the addition of 10%
trichloroacetic acid using tRNA as a carrier(32) . The
precipitated G-actin and the F-actin were solubilized in equivalent
volumes of SDS sample buffer and electrophoresed on 12%
SDS-polyacrylamide gels(33) . The amount of actin in each
sample was determined by pyridine elution of Coomassie Blue from the
stained gel slices (34) and quantitated spectroscopically by
reading the absorbance at 605 nm with reference to an actin standard
curve.
Adducin Inhibits the Polymerization and
Depolymerization of Actin from the Barbed Filament End
We used
spectrin-actin complexes (8, 31) to seed actin
polymerization in a low salt buffer (1 mM KCl, 0.4 mM Mg) where actin alone would otherwise not
polymerize(8) . Under these conditions actin polymerization is
expected to be limited to the barbed end due to the low salt
concentration as well as the presence of the pointed end actin capping
protein tropomodulin in the spectrin-actin complexes (11) . ()Fig. 1A shows that adducin dramatically
suppressed the initial rate of polymerization from the spectrin-actin
seeds. We quantitated the level of inhibition (capping) as a percentage
of the initial polymerization rate in the absence of any adducin (100%
capping indicates the complete cessation of actin polymerization).
Increasing concentrations of adducin correlated with increasing
inhibition of actin polymerization; plotting adducin concentration
against the percentage of inhibition demonstrated that saturating
concentrations of adducin can completely inhibit actin elongation from
the barbed filament end (Fig. 1B). The adducin
concentration that produced 50% capping was taken to be the K; under these conditions the K for adducin was approximately 100 nM. The inhibitory
effect of adducin on actin elongation is specific for the barbed
filament end because adducin does not inhibit the rate of elongation
from the pointed ends of gelsolin-capped actin filaments (data not
shown).
.
The initial rates of depolymerization for
actin in the presence of adducin or capping protein were 53 and 56
arbitrary units, respectively, as compared with a rate of 754 arbitrary
units for actin alone. Interestingly, after the initial period, the
rate of actin depolymerization in the presence of adducin was slower
than in the presence of capping protein. We attribute this difference
to an effect of adducin on the pointed filament end because adducin
reduced (but did not block) the rate of actin depolymerization from the
pointed ends of gelsolin capped actin filaments (data not shown). The
inhibitory effect of adducin on the rate of actin depolymerization from
the barbed filament ends also indicates that adducin does not function
by exclusively sequestering actin monomers; monomer sequestering would
have been expected to lead to an increase in the rate of actin
disassembly, which was also not observed (see below). Finally, these
data also rule out possible artifacts in the nucleated actin
polymerization assay in Fig. 1from fluorescence signal
quenching due to light scattering and demonstrate that protein
aggregation does not occur in these assays. Taken together, the ability
of adducin to inhibit both actin polymerization and depolymerization
indicates that adducin is a barbed end capping protein with a capping
affinity of 100 nM.
120
µM). This leads to the complete disassembly of the actin
filaments into monomers, as indicated by the decrease in the pyrene
fluorescence signal for the pure actin curve almost to the baseline. CP, nonmuscle capping protein.
-terminal globular head or to the COOH-terminal
extended tail domains, we tested bacterially expressed tails (24) and a head-neck domain prepared by trypsin digestion of
human erythrocyte adducin(23) . Neither the head nor the tail
domains (tested up to final concentrations of 1 and 5 µM,
respectively) had any significant effects on actin polymerization or
depolymerization in our assays (data not shown). Therefore, the barbed
end capping activity of adducin appears to be an attribute of the
entire molecule requiring both the heads and tails.The Effect of Calmodulin on the Barbed End Capping
Activity of Adducin
Calmodulin has previously been shown to bind
to adducin with a K
of 0.2-0.5 µM in the presence of calcium(18) . Calcium-dependent binding
of calmodulin to adducin prevents adducin from binding to F-actin as
well as reducing its ability to bind to spectrin-actin complexes and
recruit additional spectrin molecules to the spectrin-actin
complexes(19, 20) . Fig. 4A shows that
calmodulin in conjunction with calcium was also able to reverse the
inhibitory effect of adducin on actin polymerization from the barbed
filament end. A plot of the percentage of adducin capping activity
against calmodulin concentration produced a curve with half-maximal
reversal of capping at about 2 µM calmodulin (Fig. 4A). The ability of calmodulin to eliminate the
barbed end capping activity of adducin was also seen in actin
depolymerization experiments as evidenced by the return of the
depolymerization rate in the presence of adducin plus calmodulin to
that of pure actin (Fig. 4B).
(see ``Experimental Procedures''). B, effect
of calmodulin on the ability of adducin to inhibit the rate of actin
depolymerization in the presence of calcium. This assay was performed
as described above in Fig. 2but with diluting the F-actin into
a solution containing adducin and calmodulin to give final
concentrations of 700 nM and 10 µM, respectively.
Calmodulin had no effect on actin polymerization in the absence of
adducin (not shown).
100 nM. The association of
stoichiometric amounts of adducin with the short actin filaments in the
erythrocyte membrane skeleton (18) implies that adducin may
indeed be the functional barbed end cap in erythrocytes and supports
our hypothesis that the mechanism of restriction of actin filament
length in erythrocytes is based on capping actin filaments at both ends
to prevent growth or shrinking, similar to striated muscle. Although it
has been assumed that the barbed ends of the actin filaments in the
erythrocyte membrane skeleton are uncapped, this idea stems mainly from
the use of purified membranes or isolated spectrin-actin oligomeric
complexes to nucleate actin
polymerization(32, 37, 38, 39) . Our
results raise the possibility that the capping activity of adducin
might have been inactivated during hemolysis and/or the extraction
procedures used to prepare membranes and purify the spectrin-actin
complexes used in these experiments. = 280 nM)(20) . It
is also striking that the inhibitory effect of calmodulin on the barbed
end capping activity of adducin has a similar dependence on calmodulin
concentration as that of calmodulin's inhibition of adducin side
binding to F-actin and to spectrin-actin
complexes(19, 20) . Furthermore, the calmodulin
binding site on adducin has been proposed to be located on the
midregion of the COOH-terminal tail domains(43) ; yet
dissection of adducin into NH-terminal head and
COOH-terminal tail domains shows that the entire molecule is required
for barbed end capping activity. Therefore, the barbed end capping
activity of adducin may be functionally linked to its ability to bind
along the sides of actin filaments.-terminal head domain of the adducin
and subunits diverges significantly from the consensus
actin-binding domain found in the functional members of the
-actinin protein family (similarity: -adducin 47.9%,
-adducin 40.7%; identity: -adducin 21.6%, -adducin
12.8%). (
)In addition, both the and subunits of
adducin deviate from the sequence found in -actinin by the
presence of an extra portion of sequence; in the case of the
subunit, this is in one of the regions identified as the actin-binding
site(44) . The divergence from the consensus actin-binding
sequence has been suggested to explain the lack of binding to actin
filaments by the head domain of adducin(22) . However, we would
propose that this actin-binding site in the NH-terminal
head domain of adducin may have, through divergent evolution, developed
the capability to bind to actin so as to cap the barbed end of the
filament. Actin monomers in the filament are oriented such that
subdomains 1 and 3 are exposed at the barbed end of the actin
filament(45, 46) . It may be significant that a
portion of the -actinin actin binding site has been demonstrated
to be on subdomain 1 of actin(47, 48, 49) . -terminal head domain is reliant
on the side binding of the adducin COOH-terminal tails to actin
filaments. It is likely that the COOH-terminal tail domains of the
and subunits possess an F-actin binding site based on their
ability to bind to spectrin-actin complexes and to promote spectrin
binding to actin (24) . Binding of the tails along each strand
of the actin filament in a polarized fashion (21) could
position the head domains to bind to a site in subdomain 1 of the
terminal actin monomer at the barbed filament end, hence interfering
with association of new actin monomers as well as stabilizing the
filament and preventing monomer dissociation. A model depicting binding
of adducin tails to actin and capping the barbed end of the actin
filament by adducin heads is shown in Fig. 5. In addition to
promoting spectrin binding to actin, binding of adducin tails along the
sides of the erythrocyte actin filaments may also play a role in
stabilizing them at their pointed filament ends, as suggested by the
actin critical concentration experiment (Fig. 3). The
multifunctional actin binding properties of adducin may not be unique;
tensin is another protein that has been shown to cap actin filament
barbed ends as well as to bind along the sides of actin filaments and
bundle them(50, 51) .
-terminal actin-binding region of -spectrin
is depicted, and -spectrin, protein 4.9, protein 4.1, and the
tropomodulin and tropomyosin at the pointed end of the actin filament
have been omitted. The NH-terminal adducin head domains
form a tetramer (24) at the barbed end of the filament blocking
the exchange of actin monomers. The extended COOH-terminal adducin
tails lie along each strand of the actin filament forming contacts
between the actin and spectrin molecules, enhancing their interaction.
We propose that this lateral actin binding by the adducin tails is
responsible for maintenance of the cap at the end of the filament.
Recruitment of extra spectrin molecules is either due to increased
affinity of spectrin for the complex or the reorganization of the bound
spectrin to accommodate more molecules. Hence adducin plays a crucial
role in the organization of the molecular interactions at the barbed
end of the actin filaments in erythrocytes.
)))
We are grateful to Dr. Charles Cochrane for allowing
us to use the spectrofluorimeter and to Lydia Davis (Duke Medical
Center) for the generous gift of calmodulin. We acknowledge the Scripps
General Clinical Research Center for the provision of normal human
blood (supported by National Institutes of Health Grant M01 RR00833).
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
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 C. L. Galindo, A. A. Fadl, J. Sha, L. Pillai, C. Gutierrez Jr., and A. K. Chopra Microarray and Proteomics Analyses of Human Intestinal Epithelial Cells Treated with the Aeromonas hydrophila Cytotoxic Enterotoxin Infect. Immun., May 1, 2005; 73(5): 2628 - 2643. [Abstract] [Full Text] [PDF]
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 R. L. Rabenstein, N. A. Addy, B. J. Caldarone, Y. Asaka, L. M. Gruenbaum, L. L. Peters, D. M. Gilligan, R. M. Fitzsimonds, and M. R. Picciotto Impaired Synaptic Plasticity and Learning in Mice Lacking {beta}-Adducin, an Actin-Regulating Protein J. Neurosci., February 23, 2005; 25(8): 2138 - 2145. [Abstract] [Full Text] [PDF]
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 R. Efendiev, R. T. Krmar, G. Ogimoto, J. Zwiller, G. Tripodi, A. I. Katz, G. Bianchi, C. H. Pedemonte, and A. M. Bertorello Hypertension-Linked Mutation in the Adducin {alpha}-Subunit Leads to Higher AP2-{micro}2 Phosphorylation and Impaired Na+,K+-ATPase Trafficking in Response to GPCR Signals and Intracellular Sodium Circ. Res., November 26, 2004; 95(11): 1100 - 1108. [Abstract] [Full Text] [PDF]
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 K. L. Barkalow, J. E. Italiano Jr., D. E. Chou, Y. Matsuoka, V. Bennett, and J. H. Hartwig {alpha}-Adducin dissociates from F-actin and spectrin during platelet activation J. Cell Biol., May 12, 2003; 161(3): 557 - 570. [Abstract] [Full Text] [PDF]
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 X. Chu, J. Chen, M. C. Reedy, C. Vera, K.-L. P. Sung, and L. A. Sung E-Tmod capping of actin filaments at the slow-growing end is required to establish mouse embryonic circulation Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1827 - H1838. [Abstract] [Full Text] [PDF]
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R. S. Fischer, K. L. Fritz-Six, and V. M. Fowler Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility J. Cell Biol., April 28, 2003; 161(2): 371 - 380. [Abstract] [Full Text] [PDF]
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L. M. Gruenbaum, D. M. Gilligan, M. R. Picciotto, S. Marinesco, and T. J. Carew Identification and Characterization of Aplysia Adducin, an Aplysia Cytoskeletal Protein Homologous to Mammalian Adducins: Increased Phosphorylation at a Protein Kinase C Consensus Site during Long-Term Synaptic Facilitation J. Neurosci., April 1, 2003; 23(7): 2675 - 2685. [Abstract] [Full Text] [PDF]
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 R. Khanna, S. H. Chang, S. Andrabi, M. Azam, A. Kim, A. Rivera, C. Brugnara, P. S. Low, S.-C. Liu, and A. H. Chishti Headpiece domain of dematin is required for the stability of the erythrocyte membrane PNAS, May 14, 2002; 99(10): 6637 - 6642. [Abstract] [Full Text] [PDF]
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D. M. Gilligan, R. Sarid, and J. Weese Adducin in platelets: activation-induced phosphorylation by PKC and proteolysis by calpain Blood, April 1, 2002; 99(7): 2418 - 2426. [Abstract] [Full Text] [PDF]
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 V. Bennett and A. J. Baines Spectrin and Ankyrin-Based Pathways: Metazoan Inventions for Integrating Cells Into Tissues Physiol Rev, July 1, 2001; 81(3): 1353 - 1392. [Abstract] [Full Text] [PDF]
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A. F. Muro, M. L. Marro, S. Gajovic, F. Porro, L. Luzzatto, and F. E. Baralle Mild spherocytic hereditary elliptocytosis and altered levels of alpha - and gamma -adducins in beta -adducin-deficient mice Blood, June 15, 2000; 95(12): 3978 - 3985. [Abstract] [Full Text] [PDF]
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W. Nunomura, Y. Takakuwa, M. Parra, J. G. Conboy, and N. Mohandas Ca2+-dependent and Ca2+-independent Calmodulin Binding Sites in Erythrocyte Protein 4.1. IMPLICATIONS FOR REGULATION OF PROTEIN 4.1 INTERACTIONS WITH TRANSMEMBRANE PROTEINS J. Biol. Chem., February 25, 2000; 275(9): 6360 - 6367. [Abstract] [Full Text] [PDF]
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