title: Atypical regulation of G protein-coupled receptor intracellular trafficking by ubiquitination.
abstract: G protein-coupled receptor (GPCR) signaling is precisely regulated. After activation, GPCRs are desensitized, internalized and either recycled to the cell surface or sorted to lysosomes for degradation. The main route for GPCR lysosomal sorting requires ubiquitination and the endosomal-sorting complex required for transport (ESCRT). Four distinct ESCRT adaptor protein complexes act sequentially to bind and sort ubiquitinated cargo to lysosomes. Several studies now indicate that alternate pathways exist for GPCR lysosomal sorting that require only some components of the ESCRT and autophagy machinery. While direct GPCR ubiquitination is not required for alternate lysosomal sorting, new evidence suggests that ubiquitin may function indirectly to modulate adaptor protein activity. Here, we discuss the atypical regulation of GPCR lysosomal sorting by ubiquitination.
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Dores
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: joanntrejo@ucsd.edu.
authors.forename: JoAnn
authors.initials: J
authors.lastname: Trejo
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D050178:Monoglycerides / Q000378:metabolism; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D050178:Monoglycerides; D043562:Receptors, G-Protein-Coupled; D025801:Ubiquitin; C012786:bis(monoacylglyceryl)phosphate