Modulation of postendocytic sorting of G protein-coupled receptors.
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.
Whistler
Jennifer L
JL
Department of Neurology, Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, CA 94608, USA. shooz2@itsa.ucsf.edu
Enquist
Johan
J
Marley
Aaron
A
Fong
Jamie
J
Gladher
Fredrik
F
Tsuruda
Pamela
P
Murray
Stephen R
SR
Von Zastrow
Mark
M
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D015536:Down-Regulation; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D021381:Protein Transport; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; C463459:GPRASP1 protein, human; D018343:Receptors, Adrenergic, beta-2; D011956:Receptors, Cell Surface; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; D033921:Vesicular Transport Proteins; D066246:ErbB Receptors; D020962:Heterotrimeric GTP-Binding Proteins