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Titolo:
Subtype-specific enhancement of NMDA receptor currents by mutant Huntingtin
Autore:
Chen, NS; Luo, T; Wellington, C; Metzler, M; McCutcheon, K; Hayden, MR; Raymond, LA;
Indirizzi:
Univ British Columbia, Dept Psychiat, Div Neurosci, Kinsmen Lab, Vancouver, Univ British Columbia Vancouver BC Canada V6T 1Z3 Kinsmen Lab, Vancouver, UnivBCritish Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver,Univ British Columbia Vancouver BC Canada V6T 1Z3 & Therapeut, Vancouver, Univ British Columbia, Dept Physiol, Vancouver, BC V6T 1Z3, Canada Univ British Columbia Vancouver BC Canada V6T 1Z3 ver, BC V6T 1Z3, Canada Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC V6T 1Z3, CanadaUniv British Columbia Vancouver BC Canada V6T 1Z3 ver, BC V6T 1Z3, Canada
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 5, volume: 72, anno: 1999,
pagine: 1890 - 1898
SICI:
0022-3042(199905)72:5<1890:SEONRC>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEURONAL INTRANUCLEAR INCLUSIONS; DISEASE GENE HOMOLOG; POLYGLUTAMINE TRACT; QUINOLINIC ACID; IN-VIVO; SACCHAROMYCES-CEREVISIAE; GLUTAMATE RECEPTORS; EMBRYONIC LETHALITY; PROJECTION NEURONS; STRIATAL NEURONS;
Keywords:
Huntingtin; glutamate; patch clamp; HEK 293 cells; excitotoxicity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
72
Recensione:
Indirizzi per estratti:
Indirizzo: Raymond, LA Univesbrookh Columbia, Dept Psychiat, Div Neurosci, Kinsmen Lab, 4N3-2255 W Univ British Columbia 4N3-2255 Wesbrook Mall Vancouver BC Canada V6T 1Z3
Citazione:
N.S. Chen et al., "Subtype-specific enhancement of NMDA receptor currents by mutant Huntingtin", J NEUROCHEM, 72(5), 1999, pp. 1890-1898

Abstract

Evidence suggests that NMDA receptor-mediated neurotoxicity plays a role in the selective neurodegeneration underlying Huntington's disease (HD), Thegene mutation that causes HD encodes an expanded polyglutamine tract of >35 in huntingtin, a protein of unknown function. Both huntingtin and NMDA receptors interact with cytoskeletal proteins, and, for NMDA receptors, such interactions regulate surface expression and channel activity. To determinewhether mutant huntingtin alters NMDA receptor expression or function, we coexpressed mutant or normal huntingtin, containing 138 or 15 glutamine repeats, respectively, with NMDA receptors in a cell line and then assessed receptor channel function by patch-clamp recording and surface expression by western blot analysis. It is interesting that receptors composed of NR1 andNR2B subunits exhibited significantly larger currents when coexpressed with mutant compared with normal huntingtin, Moreover, this effect was selective for NR1/NR2B, as NR1/NR2A showed similar currents when coexpressed with mutant versus normal huntingtin. However, ion channel properties and total surface expression of the NR1 subunit were unchanged in cells cotransfectedwith NR1/NR2B and mutant huntingtin, Our results suggest that mutant huntingtin may increase numbers of functional NR1/NR2B-type receptors at the cell surface. Because NR1/NR2B is the predominant NMDA receptor subtype expressed in medium spiny neostriatal neurons, our findings may help explain the selective vulnerability of these neurons in HD.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 19:12:04