Modulation of postendocytic sorting of G protein-coupled receptors

Jennifer Whistler, Johan Enquist, Aaron Marley, Jamie Fong, Fredrik Gladher, Pamela Tsuruda, Stephen R. Murray, Mark Von Zastrow

Research output: Contribution to journalArticle

250 Scopus citations

Abstract

Recycling of the mu opioid receptor to the plasma membrane after endocytosis promotes rapid resensitization of signal transduction, whereas targeting of the delta opioid receptor (DOR) to lysosomes causes proteolytic down-regulation. We identified a protein that binds preferentially to the cytoplasmic tail of the DOR as a candidate heterotrimeric GTP-binding protein (G protein)- coupled receptor-associated sorting protein (GASP). Disruption of the DOR-GASP interaction through receptor mutation or overexpression of a dominant negative fragment of GASP inhibited receptor trafficking to lysosomes and promoted recycling. The GASP family of proteins may modulate lysosomal sorting and functional down-regulation of a variety of G protein-coupled receptors.

Original languageEnglish (US)
Pages (from-to)615-620
Number of pages6
JournalScience
Volume297
Issue number5581
DOIs
StatePublished - Jul 26 2002
Externally publishedYes

ASJC Scopus subject areas

  • General

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    Whistler, J., Enquist, J., Marley, A., Fong, J., Gladher, F., Tsuruda, P., Murray, S. R., & Von Zastrow, M. (2002). Modulation of postendocytic sorting of G protein-coupled receptors. Science, 297(5581), 615-620. https://doi.org/10.1126/science.1073308