Identification of a novel family of G protein-coupled receptor associated sorting proteins.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Central Nervous System, Chromosomes, Human, Pair 10, Cloning, Molecular, Conserved Sequence, Humans, Mice, Molecular Sequence Data, Multigene Family, Organ Specificity, Protein Binding, Protein Transport, RNA, Messenger, Receptors, G-Protein-Coupled, Receptors, Opioid, delta, Receptors, Opioid, mu, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Two-Hybrid System Techniques, Vesicular Transport Proteins
Amino Acid Sequence, Animals, Central Nervous System, Chromosomes, Human, Pair 10, Cloning, Molecular, Conserved Sequence, Humans, Mice, Molecular Sequence Data, Multigene Family, Organ Specificity, Protein Binding, Protein Transport, RNA, Messenger, Receptors, G-Protein-Coupled, Receptors, Opioid, delta, Receptors, Opioid, mu, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Two-Hybrid System Techniques, Vesicular Transport Proteins
J. Neurochem.
Date: May. 01, 2004
PubMed ID: 15086532
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