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Publication : Identification of a novel family of G protein-coupled receptor associated sorting proteins.

First Author  Simonin F Year  2004
Journal  J Neurochem Volume  89
Issue  3 Pages  766-75
PubMed ID  15086532 Mgi Jnum  J:161029
Mgi Id  MGI:4456952 Doi  10.1111/j.1471-4159.2004.02411.x
Citation  Simonin F, et al. (2004) Identification of a novel family of G protein-coupled receptor associated sorting proteins. J Neurochem 89(3):766-75
abstractText  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.
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