HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 36, 37461-37469, September 3, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/36/37461    most recent M401034200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vargas, G. A. Articles by von Zastrow, M. Search for Related Content PubMed PubMed Citation Articles by Vargas, G. A. Articles by von Zastrow, M. Social Bookmarking                      What's this?

Identification of a Novel Endocytic Recycling Signal in the D1 Dopamine Receptor^*

Gabriel A. Vargas and Mark von Zastrow¶

From the Departments of Psychiatry and ^¶Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143-2140

A critical event determining the functional consequences of G protein-coupled receptor (GPCR) endocytosis is the molecular sorting of internalized receptors between divergent recycling and degradative membrane pathways. The D1 dopamine receptor recycles rapidly and efficiently to the plasma membrane after agonist-induced endocytosis and is remarkably resistant to proteolytic down-regulation. Whereas the mechanism mediating agonist-induced endocytosis of D1 receptors has been investigated in some detail, little is known about how receptors are sorted after endocytosis. We have identified a sequence present in the carboxyl-terminal cytoplasmic domain of the human D1 dopamine receptor that is specifically required for the efficient recycling of endocytosed receptors back to the plasma membrane. This sequence is distinct from previously identified membrane trafficking signals and is located in a proximal portion of the carboxyl-terminal cytoplasmic domain, in contrast to previously identified GPCR recycling signals present at the distal tip. Nevertheless, fusion of this sequence to the carboxyl terminus of a chimeric mutant opioid neuropeptide receptor is sufficient to re-route internalized receptors from lysosomal to recycling membrane pathways, defining this sequence as a bona fide endocytic recycling signal that can function in both proximal and distal locations. These results identify a novel sorting signal controlling the endocytic trafficking itinerary of a physiologically important dopamine receptor, provide the first example of such a sorting signal functioning in a proximal portion of the carboxyl-terminal cytoplasmic domain, and suggest the existence of a diverse array of sorting signals in the GPCR superfamily that mediate subtype-specific regulation of receptors via endocytic membrane trafficking.

Received for publication, January 30, 2004 , and in revised form, June 8, 2004.

^* These studies were supported by a research grant from the National Institutes of Health (to M. v. Z.) and by a Veterans Administration Psychiatry and Neurosciences Fellowship, an American Psychiatric Research Institute Psychiatric Minority Research Training Program Research Fellowship, and NIMH Mentored Career Development K08 Award (to G. A. V.). 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.

To whom correspondence should be addressed: N-216 Genentech Hall, University of California, 600 16th St., San Francisco, CA 94143-2140. Tel.: 415-476-7871; Fax: 415-504-0169; E-mail: gvargas{at}itsa.ucsf.edu.

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

This article has been cited by other articles:

				S.-H. Huang, L. Zhao, Z.-P. Sun, X.-Z. Li, Z. Geng, K.-D. Zhang, M. V. Chao, and Z.-Y. Chen Essential Role of Hrs in Endocytic Recycling of Full-length TrkB Receptor but Not Its Isoform TrkB.T1 J. Biol. Chem., May 29, 2009; 284(22): 15126 - 15136. [Abstract] [Full Text] [PDF]

				B. E. L. Lauffer, S. Chen, C. Melero, T. Kortemme, M. von Zastrow, and G. A. Vargas Engineered Protein Connectivity to Actin Mimics PDZ-dependent Recycling of G Protein-coupled Receptors but Not Its Regulation by Hrs J. Biol. Chem., January 23, 2009; 284(4): 2448 - 2458. [Abstract] [Full Text] [PDF]

				F. Wang, X. Chen, X. Zhang, and L. Ma Phosphorylation State of {micro}-Opioid Receptor Determines the Alternative Recycling of Receptor via Rab4 or Rab11 Pathway Mol. Endocrinol., August 1, 2008; 22(8): 1881 - 1892. [Abstract] [Full Text] [PDF]

				Y. Hashimoto, K. Morisawa, H. Saito, E. Jojima, N. Yoshida, and T. Haga Muscarinic M4 Receptor Recycling Requires a Motif in the Third Intracellular Loop J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 947 - 953. [Abstract] [Full Text] [PDF]

				X. Sun, M. Milovanovic, Y. Zhao, and M. E. Wolf Acute and Chronic Dopamine Receptor Stimulation Modulates AMPA Receptor Trafficking in Nucleus Accumbens Neurons Cocultured with Prefrontal Cortex Neurons J. Neurosci., April 16, 2008; 28(16): 4216 - 4230. [Abstract] [Full Text] [PDF]

				B. Wang, A. Bisello, Y. Yang, G. G. Romero, and P. A. Friedman NHERF1 Regulates Parathyroid Hormone Receptor Membrane Retention without Affecting Recycling J. Biol. Chem., December 14, 2007; 282(50): 36214 - 36222. [Abstract] [Full Text] [PDF]

				M. Delhaye, A. Gravot, D. Ayinde, F. Niedergang, M. Alizon, and A. Brelot Identification of a Postendocytic Sorting Sequence in CCR5 Mol. Pharmacol., December 1, 2007; 72(6): 1497 - 1507. [Abstract] [Full Text] [PDF]

				D. Thompson, M. Pusch, and J. L. Whistler Changes in G Protein-coupled Receptor Sorting Protein Affinity Regulate Postendocytic Targeting of G Protein-coupled Receptors J. Biol. Chem., October 5, 2007; 282(40): 29178 - 29185. [Abstract] [Full Text] [PDF]

				B. Hasdemir, N. W. Bunnett, and G. S. Cottrell Hepatocyte Growth Factor-regulated Tyrosine Kinase Substrate (HRS) Mediates Post-endocytic Trafficking of Protease-activated Receptor 2 and Calcitonin Receptor-like Receptor J. Biol. Chem., October 5, 2007; 282(40): 29646 - 29657. [Abstract] [Full Text] [PDF]

				A. C. Hanyaloglu and M. von Zastrow A Novel Sorting Sequence in the beta2-Adrenergic Receptor Switches Recycling from Default to the Hrs-dependent Mechanism J. Biol. Chem., February 2, 2007; 282(5): 3095 - 3104. [Abstract] [Full Text] [PDF]

				Z.-Y. Chen, A. Ieraci, M. Tanowitz, and F. S. Lee A Novel Endocytic Recycling Signal Distinguishes Biological Responses of Trk Neurotrophin Receptors Mol. Biol. Cell, December 1, 2005; 16(12): 5761 - 5772. [Abstract] [Full Text] [PDF]

				E. Hamelin, C. Theriault, G. Laroche, and J.-L. Parent The Intracellular Trafficking of the G Protein-coupled Receptor TP{beta} Depends on a Direct Interaction with Rab11 J. Biol. Chem., October 28, 2005; 280(43): 36195 - 36205. [Abstract] [Full Text] [PDF]

				J. P. Ryman-Rasmussen, D. E. Nichols, and R. B. Mailman Differential Activation of Adenylate Cyclase and Receptor Internalization by Novel Dopamine D1 Receptor Agonists Mol. Pharmacol., October 1, 2005; 68(4): 1039 - 1048. [Abstract] [Full Text] [PDF]