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Identification of a novel family of G protein‐coupled receptor associated sorting proteins
Author(s) -
Simonin Frederic,
Karcher Pascale,
Boeuf Julien J.M.,
Matifas Audrey,
Kieffer Brigitte L.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02411.x
Subject(s) - g protein coupled receptor , receptor , biology , rhodopsin , rhodopsin like receptors , protein–protein interaction , protein targeting , protein family , g protein , computational biology , microbiology and biotechnology , genetics , gene , membrane protein , biochemistry , glutamate receptor , retinal , metabotropic receptor , membrane
During the past few years several new interacting partners for G protein‐coupled receptors (GPCRs) have been discovered, suggesting that the activity of these receptors is more complex than previously anticipated. Recently, candidate G protein‐coupled receptor associated sorting protein (GASP‐1) has been identified as a novel interacting partner for the delta opioid receptor and has been proposed to determine the degradative fate of this receptor. We show here that GASP‐1 associates in vitro with other opioid receptors and that the interaction domain in these receptors is restricted to a small portion of the carboxyl‐terminal tail, corresponding to helix 8 in the three‐dimensional structure of rhodopsin. In addition, we show that GASP‐1 interacts with COOH‐terminus of several other GPCRs from subfamilies A and B and that two conserved residues within the putative helix 8 of these receptors are critical for the interaction with GASP‐1. In situ hybridization and northern blot analysis indicate that GASP‐1 mRNA is mainly distributed throughout the central nervous system, consistent with a potential interaction with numerous GPCRs in vivo . Finally, we show that GASP‐1 is a member of a novel family comprising at least 10 members, whose genes are clustered on chromosome X. Another member of the family, GASP‐2, also interacts with the carboxyl‐terminal tail of several GPCRs. Therefore, GASP proteins may represent an important protein family regulating GPCR physiology.