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Titolo:
Multiple topological domains mediate subtype-specific internalization of the M-2 muscarinic acetylcholine receptor
Autore:
Schlador, ML; Grubbs, RD; Nathanson, NM;
Indirizzi:
Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 ept Pharmacol, Seattle, WA 98195 USA Wright State Univ, Sch Med, Dept Pharmacol & Toxicol, Dayton, OH 45435 USAWright State Univ Dayton OH USA 45435 col & Toxicol, Dayton, OH 45435 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 30, volume: 275, anno: 2000,
pagine: 23295 - 23302
SICI:
0021-9258(20000728)275:30<23295:MTDMSI>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-COUPLED RECEPTORS; BETA(2)-ADRENERGIC RECEPTOR; BETA-ARRESTIN; DIFFERENTIAL REGULATION; INDEPENDENT MECHANISMS; ADENYLYL-CYCLASE; DOWN-REGULATION; M2; ENDOCYTOSIS; AGONIST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Nathanson, NM Univ Washington, Sch Med, Dept Pharmacol, Box 357750, Seattle, WA 98195 USA Univ Washington Box 357750 Seattle WA USA 98195 WA 98195 USA
Citazione:
M.L. Schlador et al., "Multiple topological domains mediate subtype-specific internalization of the M-2 muscarinic acetylcholine receptor", J BIOL CHEM, 275(30), 2000, pp. 23295-23302

Abstract

Endocytosis of agonist-activated G protein-coupled receptors (GPCRs) is required for both resensitization and recycling to the cell surface as well as lysosomal degradation. Thus, this process is crucial for regulation of receptor signaling and cellular responsiveness. Although many GPCRs internalize into clathrin-coated vesicles in a dynamin-dependent manner, some receptors, including the M-2 muscarinic acetylcholine receptor (mAChR), can also exhibit dynamin-independent internalization. We have identified five amino acids, located in the sixth and seventh transmembrane domains and the thirdintracellular loop, that are essential for agonist-induced M-2 mAChR internalization via a dynamin-independent mechanism in JEG-3 choriocarcinoma cells. Substitution of these residues into the M-1 mAChR, which does not internalize in these cells, is sufficient for conversion to the internalization-competent M-2 mAChR phenotype, whereas removal of these residues from the M-2 mAChR blocks internalization. Cotransfection of a dominant-negative isoform of dynamin has no effect on M-2 mAChR internalization. An internalization-incompetent M-2 mutant that lacks a subset of the necessary residues canstill internalize via a G protein-coupled receptor kinase-2 and beta-arrestin-dependent pathway. Furthermore, internalization is independent of the signal transduction pathway that is activated. These results identify a novel motif that specifies structural requirements for subtype-specific dynamin-independent internalization of a GPCR.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 20:04:20