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Titolo:
Functional alterations in gap junction channels formed by mutant forms of connexin 32: evidence for loss of function as a pathogenic mechanism in theX-linked form of Charcot-Marie-Tooth disease
Autore:
Abrams, CK; Freidin, MM; Verselis, VK; Bennett, MVL; Bargiello, TA;
Indirizzi:
Albert Einstein Coll Med, Bronx, NY 10463 USA Albert Einstein Coll Med Bronx NY USA 10463 Coll Med, Bronx, NY 10463 USA
Titolo Testata:
BRAIN RESEARCH
fascicolo: 1, volume: 900, anno: 2001,
pagine: 9 - 25
SICI:
0006-8993(20010504)900:1<9:FAIGJC>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
VOLTAGE DEPENDENCE; MUTATIONS; GENE; CONDUCTANCE; NEUROPATHY; CELLS; FAMILY; HEMICHANNEL; PROTEIN; CMTX1;
Keywords:
connexin 32; loss of function; Charcot-Marie-Tooth disease; peripheral neuropathy; conductance-voltage relations; Xenopus oocyte expression system;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Abrams, CK Albert Einstein Coll Med, 1300 Morris Pk Ave, Bronx, NY 10463 USA Albert Einstein Coll Med 1300 Morris Pk Ave Bronx NY USA 10463
Citazione:
C.K. Abrams et al., "Functional alterations in gap junction channels formed by mutant forms of connexin 32: evidence for loss of function as a pathogenic mechanism in theX-linked form of Charcot-Marie-Tooth disease", BRAIN RES, 900(1), 2001, pp. 9-25

Abstract

CMTX, the X-linked form of Charcot-Marie-Tooth disease, is an inherited peripheral neuropathy arising in patients with mutations in the gene encodingthe gap junction protein connexin 32 (Cx32). In this communication, we describe the expression levels and biophysical parameters of seven mutant forms of Cx32 associated with CMTX, when expressed in paired Xenopus oocytes. Paired oocytes expressing the R15Q and H94Q mutants show junctional conductances not statistically different from that determined for Cx32WT, though both show a trend toward reduced levels. The S85C and G12S mutants induce reduced levels of junctional conductance. Three other mutants (R15W. H94Y and V139M) induce no conductance above baseline when expressed in paired oocytes. Analysis of the conductance voltage relations for these mutants shows that the reduced levels of conductance are entirely (H94Y and V139M) or partly (S85C and R15W) explicable by a reduced open probability of the mutant hemichannels, The R15Q and H94Q mutations also show alterations in the conductance voltage relations that would be expected to minimally (H94Q) or moderately (R15Q) reduce the available gap junction communication pathway. The reduction in G12S induced conductance cannot be explained by alterations in hemichannel open probability and are more likely due to reduced junction formation. These results demonstrate that many CMTX mutations lead to loss offunction of Cx32. For these mutations, the loss of function model is likely to explain the pathogenesis of CMTX. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 18:06:29