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

245 Citations (Scopus)

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

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delta Opioid Receptor
G-Protein-Coupled Receptors
Recycling
Lysosomes
Down-Regulation
Heterotrimeric GTP-Binding Proteins
mu Opioid Receptor
Protein Transport
Endocytosis
Signal Transduction
Proteins
Cell Membrane
Mutation

ASJC Scopus subject areas

  • General

Cite this

Whistler, J., Enquist, J., Marley, A., Fong, J., Gladher, F., Tsuruda, P., ... 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

Modulation of postendocytic sorting of G protein-coupled receptors. / Whistler, Jennifer; Enquist, Johan; Marley, Aaron; Fong, Jamie; Gladher, Fredrik; Tsuruda, Pamela; Murray, Stephen R.; Von Zastrow, Mark.

In: Science, Vol. 297, No. 5581, 26.07.2002, p. 615-620.

Research output: Contribution to journalArticle

Whistler, J, Enquist, J, Marley, A, Fong, J, Gladher, F, Tsuruda, P, Murray, SR & Von Zastrow, M 2002, 'Modulation of postendocytic sorting of G protein-coupled receptors', Science, vol. 297, no. 5581, pp. 615-620. https://doi.org/10.1126/science.1073308
Whistler J, Enquist J, Marley A, Fong J, Gladher F, Tsuruda P et al. Modulation of postendocytic sorting of G protein-coupled receptors. Science. 2002 Jul 26;297(5581):615-620. https://doi.org/10.1126/science.1073308
Whistler, Jennifer ; Enquist, Johan ; Marley, Aaron ; Fong, Jamie ; Gladher, Fredrik ; Tsuruda, Pamela ; Murray, Stephen R. ; Von Zastrow, Mark. / Modulation of postendocytic sorting of G protein-coupled receptors. In: Science. 2002 ; Vol. 297, No. 5581. pp. 615-620.
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