The Postendocytotic Trafficking of the Human Lutropin Receptor Is Mediated by a Transferable Motif Consisting of the C-Terminal Cysteine and an Upstream Leucine

Colette Galet; Takashi Hirakawa; Mario Ascoli

doi:10.1210/me.2003-0293

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The Postendocytotic Trafficking of the Human Lutropin Receptor Is Mediated by a Transferable Motif Consisting of the C-Terminal Cysteine and an Upstream Leucine

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The Postendocytotic Trafficking of the Human Lutropin Receptor Is Mediated by a Transferable Motif Consisting of the C-Terminal Cysteine and an Upstream Leucine

Colette Galet, Takashi Hirakawa and Mario Ascoli

Molecular endocrinology (Baltimore, Md.), Vol.18(2), pp.434-446

02/01/2004

DOI: 10.1210/me.2003-0293

PMID: 14605099

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Abstract

Abstract Mutants of the human (h) lutropin receptor (LHR) were analyzed using a combination of biochemical and imaging approaches to define motifs that participate in the postendocytotic sorting of this G protein-coupled receptor (GPCR). We show that a substantial portion of the human chorionic gonadotropin internalized by the hLHR sorts to a recycling pathway, and the internalized hLHR accumulates in endosomes because of the C-terminal cysteine (Cys699) and an upstream Leu683 present in the hLHR. The removal or simultaneous mutation of these two residues reroutes the internalized human chorionic gonadotropin to a degradation pathway and the internalized hLHR to lysosomes. We also show that grafting the 17 C-terminal residues of the hLHR into the C-terminal tail of two GPCRs that are routed to a lysosomal/degradation pathway (the rat LHR or the murine δ opioid receptor) reroutes them to an endosomal/recycling pathway. This is due to the Leu683 and Cys699 combination and another recycling motif (Gly687Thr688) that was previously identified in the hLHR. The importance of both motifs can be readily ascertained in the context of a murine δ opioid receptor/hLHR chimera. The importance of the Gly687Thr688 motif is revealed mostly in the context of a rat LHR/hLHR chimera. These studies define a novel, noncontiguous, transferable motif that participates in the sorting of internalized GPCRs.

Details

Title: Subtitle: The Postendocytotic Trafficking of the Human Lutropin Receptor Is Mediated by a Transferable Motif Consisting of the C-Terminal Cysteine and an Upstream Leucine
Creators: Colette Galet - University of Iowa
Takashi Hirakawa - University of Iowa
Mario Ascoli - University of Iowa
Resource Type: Journal article
Publication Details: Molecular endocrinology (Baltimore, Md.), Vol.18(2), pp.434-446
DOI: 10.1210/me.2003-0293
PMID: 14605099
NLM abbreviation: Mol Endocrinol
ISSN: 0888-8809
eISSN: 1944-9917
Publisher: Oxford University Press
Number of pages: 13
Language: English
Date published: 02/01/2004
Academic Unit: Injury Prevention Research Center; Neuroscience and Pharmacology; University of Iowa Health Care
Record Identifier: 9985137928202771

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