Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M408154200 on August 19, 2004

J. Biol. Chem., Vol. 279, Issue 45, 47254-47263, November 5, 2004
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
279/45/47254    most recent
M408154200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wüller, S.
Right arrow Articles by Oksche, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wüller, S.
Right arrow Articles by Oksche, A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Pharmacochaperones Post-translationally Enhance Cell Surface Expression by Increasing Conformational Stability of Wild-type and Mutant Vasopressin V2 Receptors*{boxs}

Stefan Wüller{ddagger}§, Burkhard Wiesner{ddagger}, Anja Löffler¶, Jens Furkert{ddagger}, Gerd Krause{ddagger}, Ricardo Hermosilla{ddagger}, Michael Schaefer¶, Ralf Schülein{ddagger}, Walter Rosenthal{ddagger}, and Alexander Oksche{ddagger}¶||

From the {ddagger}Forschungsinstitut für Molekulare Pharmakologie, Campus Berlin Buch, Robert-Roessle-Str. 10, 13125 Berlin, Germany, the §Kinderklinik der RWTH-Aachen, Pauwelsstr. 30, 52074 Aachen, Germany, and the Institut für Pharmakologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Thielallee 67-73, 14195 Berlin, Germany

Some membrane-permeable antagonists restore cell surface expression of misfolded receptors retained in the endoplasmic reticulum (ER) and are therefore termed pharmacochaperones. Whether pharmacochaperones increase protein stability, thereby preventing rapid degradation, or assist folding via direct receptor interactions or interfere with quality control components remains elusive. We now show that the cell surface expression and function (binding of the agonist) of the mainly ER-retained wild-type murine vasopressin V2 receptor GFP fusion protein (mV2R·GFP) is restored by the vasopressin receptor antagonists SR49059 and SR121463B with EC50 values similar to their KD values. This effect was preserved when protein synthesis was abolished. In addition, SR121463B rescued eight mutant human V2Rs (hV2Rs, three are responsible for nephrogenic diabetes insipidus) characterized by amino acid exchanges at the C-terminal end of transmembrane helix TM I and TM VII. In contrast, mutants with amino acid exchanges at the interface of TM II and IV were not rescued by either antagonist. The mechanisms involved in successful rescue of cell surface delivery are explained in a three-dimensional homology model of the antagonist-bound hV2R.

Received for publication, July 19, 2004 , and in revised form, August 19, 2004.

* The work was supported by the Deutsche Forschungsgemeinschaft (GK276/2) and the Fonds der Chemischen Industrie. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{boxs} The on-line version of this article (available at http://www.jbc.org) contains Supplementary Materials.

|| To whom correspondence should be addressed: Thielallee 67-73, 14195 Berlin, Germany. Tel.: 49-30-8445-1860; Fax: 49-30-8445-1818; E-mail: alexander.oksche{at}medizin.fu-berlin.de.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
E. White, J. McKenna, A. Cavanaugh, and G. E. Breitwieser
Pharmacochaperone-Mediated Rescue of Calcium-Sensing Receptor Loss-of-Function Mutants
Mol. Endocrinol., July 1, 2009; 23(7): 1115 - 1123.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. V. Kenny, S. L. Cousins, L. Pinho, and F. A. Stephenson
The Integrity of the Glycine Co-agonist Binding Site of N-Methyl-D-aspartate Receptors Is a Functional Quality Control Checkpoint for Cell Surface Delivery
J. Biol. Chem., January 2, 2009; 284(1): 324 - 333.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
I. Schwieger, K. Lautz, E. Krause, W. Rosenthal, B. Wiesner, and R. Hermosilla
Derlin-1 and p97/Valosin-Containing Protein Mediate the Endoplasmic Reticulum-Associated Degradation of Human V2 Vasopressin Receptors
Mol. Pharmacol., March 1, 2008; 73(3): 697 - 708.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
J. Piontek, L. Winkler, H. Wolburg, S. L. Muller, N. Zuleger, C. Piehl, B. Wiesner, G. Krause, and I. E. Blasig
Formation of tight junction: determinants of homophilic interaction between classic claudins
FASEB J, January 1, 2008; 22(1): 146 - 158.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
P. M. Conn, A. Ulloa-Aguirre, J. Ito, and J. A. Janovick
G Protein-Coupled Receptor Trafficking in Health and Disease: Lessons Learned to Prepare for Therapeutic Mutant Rescue in Vivo
Pharmacol. Rev., September 1, 2007; 59(3): 225 - 250.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. T. Leskela, P. M. H. Markkanen, E. M. Pietila, J. T. Tuusa, and U. E. Petaja-Repo
Opioid Receptor Pharmacological Chaperones Act by Binding and Stabilizing Newly Synthesized Receptors in the Endoplasmic Reticulum
J. Biol. Chem., August 10, 2007; 282(32): 23171 - 23183.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Oueslati, R. Hermosilla, E. Schonenberger, V. Oorschot, M. Beyermann, B. Wiesner, A. Schmidt, J. Klumperman, W. Rosenthal, and R. Schulein
Rescue of a Nephrogenic Diabetes Insipidus-causing Vasopressin V2 Receptor Mutant by Cell-penetrating Peptides
J. Biol. Chem., July 13, 2007; 282(28): 20676 - 20685.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z.-L. Lu, M. Coetsee, C. D. White, and R. P. Millar
Structural Determinants for Ligand-Receptor Conformational Selection in a Peptide G Protein-coupled Receptor
J. Biol. Chem., June 15, 2007; 282(24): 17921 - 17929.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. M. Clancy, S. B. Boyer, and P. A. Slesinger
Coregulation of Natively Expressed Pertussis Toxin-Sensitive Muscarinic Receptors with G-Protein-Activated Potassium Channels
J. Neurosci., June 13, 2007; 27(24): 6388 - 6399.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. Kleinau, M. Claus, H. Jaeschke, S. Mueller, S. Neumann, R. Paschke, and G. Krause
Contacts between Extracellular Loop Two and Transmembrane Helix Six Determine Basal Activity of the Thyroid-stimulating Hormone Receptor
J. Biol. Chem., January 5, 2007; 282(1): 518 - 525.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. H. Robben, M. Sze, N. V. A. M. Knoers, and P. M. T. Deen
Functional rescue of vasopressin V2 receptor mutants in MDCK cells by pharmacochaperones: relevance to therapy of nephrogenic diabetes insipidus
Am J Physiol Renal Physiol, January 1, 2007; 292(1): F253 - F260.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. H. Robben, N. V. A. M. Knoers, and P. M. T. Deen
Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus.
Am J Physiol Renal Physiol, August 1, 2006; 291(2): F257 - F270.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. R. Hawtin
Pharmacological Chaperone Activity of SR49059 to Functionally Recover Misfolded Mutations of the Vasopressin V1a Receptor
J. Biol. Chem., May 26, 2006; 281(21): 14604 - 14614.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. M. Korkhov, M. Holy, M. Freissmuth, and H. H. Sitte
The Conserved Glutamate (Glu136) in Transmembrane Domain 2 of the Serotonin Transporter Is Required for the Conformational Switch in the Transport Cycle
J. Biol. Chem., May 12, 2006; 281(19): 13439 - 13448.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
P. M. Apaja, J. T. Tuusa, E. M. Pietila, H. J. Rajaniemi, and U. E. Petaja-Repo
Luteinizing Hormone Receptor Ectodomain Splice Variant Misroutes the Full-Length Receptor into a Subcompartment of the Endoplasmic Reticulum
Mol. Biol. Cell, May 1, 2006; 17(5): 2243 - 2255.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
V. Bernier, J.-P. Morello, A. Zarruk, N. Debrand, A. Salahpour, M. Lonergan, M.-F. Arthus, A. Laperriere, R. Brouard, M. Bouvier, et al.
Pharmacologic Chaperones as a Potential Treatment for X-Linked Nephrogenic Diabetes Insipidus
J. Am. Soc. Nephrol., January 1, 2006; 17(1): 232 - 243.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Robert, C. Auzan, M. A. Ventura, and E. Clauser
Mechanisms of Cell-surface Rerouting of an Endoplasmic Reticulum-retained Mutant of the Vasopressin V1b/V3 Receptor by a Pharmacological Chaperone
J. Biol. Chem., December 23, 2005; 280(51): 42198 - 42206.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
K. Liu, T. Yang, P. C. Viswanathan, and D. M. Roden
New Mechanism Contributing to Drug-Induced Arrhythmia: Rescue of a Misprocessed LQT3 Mutant
Circulation, November 22, 2005; 112(21): 3239 - 3246.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. Tunaru, J. Lattig, J. Kero, G. Krause, and S. Offermanns
Characterization of Determinants of Ligand Binding to the Nicotinic Acid Receptor GPR109A (HM74A/PUMA-G)
Mol. Pharmacol., November 1, 2005; 68(5): 1271 - 1280.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
T. M. Fujiwara and D. G. Bichet
Molecular Biology of Hereditary Diabetes Insipidus
J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2836 - 2846.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
P. M. Apaja, J. T. Aatsinki, H. J. Rajaniemi, and U. E. Petaja-Repo
Expression of the Mature Luteinizing Hormone Receptor in Rodent Urogenital and Adrenal Tissues Is Developmentally Regulated at a Posttranslational Level
Endocrinology, August 1, 2005; 146(8): 3224 - 3232.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. M. Pietila, J. T. Tuusa, P. M. Apaja, J. T. Aatsinki, A. E. Hakalahti, H. J. Rajaniemi, and U. E. Petaja-Repo
Inefficient Maturation of the Rat Luteinizing Hormone Receptor: A PUTATIVE WAY TO REGULATE RECEPTOR NUMBERS AT THE CELL SURFACE
J. Biol. Chem., July 15, 2005; 280(28): 26622 - 26629.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement