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

J. Biol. Chem., Vol. 282, Issue 41, 30246-30255, October 12, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/41/30246    most recent M703205200v1 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 Luo, W. Articles by Reiser, G. Search for Related Content PubMed PubMed Citation Articles by Luo, W. Articles by Reiser, G. Social Bookmarking                      What's this?

p24A, a Type I Transmembrane Protein, Controls ARF1-dependent Resensitization of Protease-activated Receptor-2 by Influence on Receptor Trafficking^*

From the Institut für Neurobiochemie, Medizinische Fakultät, Otto-von-Guericke-Universität Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany

Protease-activated receptor-2 (PAR-2), the second member of the G protein-coupled PAR family, is irreversibly activated by trypsin or tryptase and then targeted to lysosomes for degradation. Intracellular presynthesized receptors stored at the Golgi apparatus repopulate the cell surface after trypsin stimulation, thereby leading to rapid resensitization to trypsin signaling. However, the molecular mechanisms of the exocytic trafficking of PAR-2 from the Golgi apparatus to the plasma membrane remain largely unclear. Here we show that p24A, a type I transmembrane protein, which is a crucial constituent of the Golgi apparatus, associates with PAR-2 at the Golgi apparatus. The protein interaction occurs between the N-terminal region of p24A (residues 1-105; p24A-GL (GOLD domain with a small linker)) and the second extracellular loop of PAR-2. After receptor activation, PAR-2 dissociates from p24A. Importantly, we found that ADP-ribosylation factor 1 regulated the dissociation process and initiated PAR-2 trafficking to the plasma membrane. Conversely, overexpression of the fragment p24A-GL, but not other mutants containing the functional coiled-coil domain of p24A, arrested PAR-2 at the Golgi apparatus and inhibited receptor trafficking to the plasma membrane, which consequently prevented resensitization of PAR-2. These findings identify a new function of p24A as a regulator of signal-dependent trafficking that regulates the life cycle of PAR-2, Thus, we reveal a new molecular mechanism underlying resensitization of PAR-2.

Received for publication, April 16, 2007 , and in revised form, July 23, 2007.

^* 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Experimental Procedures, additional references, and Figs. 1 and 2.

¹ Both authors contributed equally to this work.

² To whom correspondence should be addressed. Tel.: 49-391-6713088; Fax: 49-391-6713097; E-mail: georg.reiser{at}med.ovgu.de.

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

This article has been cited by other articles:

				L. Achour, M. G. H. Scott, H. Shirvani, A. Thuret, G. Bismuth, C. Labbe-Jullie, and S. Marullo CD4-CCR5 interaction in intracellular compartments contributes to receptor expression at the cell surface Blood, February 26, 2009; 113(9): 1938 - 1947. [Abstract] [Full Text] [PDF]