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Titolo:
The G-protein-coupled receptor kinase GRK4 mediates homologous desensitization of metabotropic glutamate receptor 1
Autore:
Sallese, M; Salvatore, L; DUrbano, E; Sala, G; Storto, M; Launey, T; Nicoletti, F; Knopfel, T; De Blasi, A;
Indirizzi:
Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Mol Pharmacol & Pathol, I-66030 Santa Maria Imbaro, Italy Ist Ric Farmacol Mario NegriSanta Maria Imbaro Italy I-66030 aro, Italy RIKEN, Brain Sci Inst, Wako, Saitama 35101, Japan RIKEN Wako Saitama Japan 35101 Brain Sci Inst, Wako, Saitama 35101, Japan INM Neuromed, Pozzilli, Italy INM Neuromed Pozzilli ItalyINM Neuromed, Pozzilli, Italy
Titolo Testata:
FASEB JOURNAL
fascicolo: 15, volume: 14, anno: 2000,
pagine: 2569 - 2580
SICI:
0892-6638(200012)14:15<2569:TGRKGM>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBELLAR PURKINJE-CELLS; LONG-TERM DEPRESSION; SPLICE VARIANTS; RGS PROTEINS; IDENTIFICATION; EXPRESSION; MGLUR1; MICE; PHOSPHORYLATION; LOCALIZATION;
Keywords:
Purkinje cells; mGlu(1) receptor; receptor internalization; GRK; antisense knock down;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: De Blasi, A Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Mol Pharmacol & Pathol, Via Nazl, I-66030 Santa Maria Imbaro, Italy Ist RicFarmacol Mario Negri Via Nazl Santa Maria Imbaro Italy I-66030
Citazione:
M. Sallese et al., "The G-protein-coupled receptor kinase GRK4 mediates homologous desensitization of metabotropic glutamate receptor 1", FASEB J, 14(15), 2000, pp. 2569-2580

Abstract

G-protein-coupled receptor kinases (GRKs) are involved in the regulation of many G-protein-coupled receptors. As opposed to the other GRKs, such as rhodopsin kinase (GRK1) or beta -adrenergic receptor kinase (beta ARK, GRK2), no receptor substrate for GRK4 has been so far identified. Here we show that GRK4 is expressed in cerebellar Purkinje cells, where it regulates mGlu(1) metabotropic glutamate receptors, as indicated by the following: I) When coexpressed in heterologous cells (HEK293), mGlu(1) receptor signaling was desensitized by GRK4 in an agonist-dependent manner (homologous desensitization). 2) In transfected HEK293 and in cultured Purkinje cells, the exposure to glutamate agonists induced internalization of the receptor and redistribution of GRK4. There was a substantial colocalization of the receptor and kinase both under basal condition and after internalization. 3) Kinase activity was necessary for desensitizing mGlu(1a) receptor and agonist-dependent phosphorylation of this receptor was also documented. 4) Antisense treatment of cultured Purkinje cells, which significantly reduced the levels of GRK4 expression, induced a marked modification of the mGlu(1)-mediated functional response, consistent with an impaired receptor desensitization. The critical role for GRK4 in regulating mGlu(1) receptors implicates a majorinvolvement of this kinase in the physiology of Purkinje cell, and in motor learning.

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Documento generato il 29/03/20 alle ore 15:20:52