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Titolo:
Insulin promotes rapid delivery of N-methyl-D-aspartate receptors to the cell surface by exocytosis
Autore:
Skeberdis, VA; Lan, JY; Zheng, X; Zukin, RS; Bennett, MVL;
Indirizzi:
Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA Albert Einstein Coll Med Bronx NY USA 10461 Neurosci, Bronx, NY 10461 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 6, volume: 98, anno: 2001,
pagine: 3561 - 3566
SICI:
0027-8424(20010313)98:6<3561:IPRDON>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; LONG-TERM POTENTIATION; NMDA RECEPTOR; XENOPUS OOCYTES; RAT HIPPOCAMPUS; OPEN PROBABILITY; AMPA RECEPTORS; PHOSPHORYLATION; MODULATION; GLUTAMATE;
Keywords:
insulin receptor tyrosine kinase; regulated exocytosis; Xenopus oocytes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Bennett, MVL Albert Einstein Coll Med, Dept Neurosci, 1300 Morris Pk Ave, Bronx, NY 10461 USA Albert Einstein Coll Med 1300 Morris Pk Ave Bronx NY USA 10461
Citazione:
V.A. Skeberdis et al., "Insulin promotes rapid delivery of N-methyl-D-aspartate receptors to the cell surface by exocytosis", P NAS US, 98(6), 2001, pp. 3561-3566

Abstract

Insulin potentiates N-methyl-D-aspartate receptors (NMDARs) in neurons andXenopus oocytes expressing recombinant NMDARs. The present study shows that insulin induced (i) an increase in channel number times open probability (nP(o)) in outside-out patches excised from Xenopus oocytes, with no changein mean open time, unitary conductance, or reversal potential, indicating an increase in n and/or P-o; (ii) an increase in charge transfer during block of NMDA-elicited currents by the open channel blocker MK-801, indicatingincreased number of functional NMDARs in the cell membrane with no change in P-o; and (iii) increased NR1 surface expression, as indicated by Westernblot analysis of surface proteins. Botulinum neurotoxin A greatly reduced insulin potentiation, indicating that insertion of new receptors occurs viaSNARE-dependent. exocytosis. Thus, insulin potentiation occurs via delivery of new channels to the plasma membrane. NMDARs assembled from mutant subunits lacking all known sites of tyrosine and serine/threonine phosphorylation in their carboxyl-terminal tails exhibited robust insulin potentiation, suggesting that insulin potentiation does not require direct phosphorylation of NMDAR subunits. Because insulin and insulin receptors are localized toglutamatergic synapses in the hippocampus, insulin-regulated trafficking of NMDARs may play a role in synaptic transmission and plasticity, includinglong-term potentiation.

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Documento generato il 07/07/20 alle ore 12:29:46