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Titolo:
The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients
Autore:
Joutel, A; Andreux, F; Gaulis, S; Domenga, V; Cecillon, M; Battail, N; Piga, N; Chapon, F; Godfrain, C; Tournier-Lasserve, E;
Indirizzi:
Fac Med Necker Enfants Malades, INSERM, U25, F-75730 Paris, France Fac MedNecker Enfants Malades Paris France F-75730 -75730 Paris, France Hop Lariboisiere, Lab Cytogenet, F-75010 Paris, France Hop Lariboisiere Paris France F-75010 b Cytogenet, F-75010 Paris, France bioMerieux, Dept Rech & Dev Immunoassays, F-69280 Marcy LEtoile, France bioMerieux Marcy LEtoile France F-69280 s, F-69280 Marcy LEtoile, France Ctr Hosp Reg & Univ Caen, Neuropathol Lab, F-14033 Caen, France Ctr Hosp Reg & Univ Caen Caen France F-14033 l Lab, F-14033 Caen, France Clin Univ St Luc, Neuropathol Lab, B-1200 Brussels, Belgium Clin Univ St Luc Brussels Belgium B-1200 l Lab, B-1200 Brussels, Belgium
Titolo Testata:
JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 5, volume: 105, anno: 2000,
pagine: 597 - 605
SICI:
0021-9738(200003)105:5<597:TEOTNR>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
AUTOSOMAL-DOMINANT ARTERIOPATHY; SUBCORTICAL INFARCTS; LEUKOENCEPHALOPATHY; STROKE; EXPRESSION; MUTATIONS; PATTERNS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Joutel, A Fac Med Necker Enfants Malades, INSERM, U25, 156 Rue Vaugirard, F-75730 Paris, France Fac Med Necker Enfants Malades 156 Rue Vaugirard Paris France F-75730
Citazione:
A. Joutel et al., "The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients", J CLIN INV, 105(5), 2000, pp. 597-605

Abstract

Mutations in Notch3 cause CADASIL (cerebral autosomal dominant adult onsetarteriopathy), which leads to stroke and dementia in humans. CADASIL arteriopathy is characterized by major alterations of vascular smooth muscle cells and the presence of specific granular osmiophilic deposits. Patients carry highly stereotyped mutations that lead to an odd number of cysteine residues within EGF-like repeats of the Notch3 receptor extracellular domain. Such mutations may alter the processing or the trafficking of this receptor,or may favor its oligomerization. In this study, we examined the Notch3 expression pattern in normal tissues and investigated the consequences of mutations on Notch3 expression in transfected cells and CADASIL brains. In normal tissues, Notch3 expression is restricted to vascular smooth muscle cells. Notch3 undergoes a proteolytic cleavage leading to a 210-kDa extracellular fragment and a 97-kDa intracellular fragment. In CADASIL brains, we found evidence of a dramatic and selective accumulation of the 210-kDa Notch3 cleavage product. Notch3 accumulates at the cytoplasmic membrane of vascularsmooth muscle cells, in close vicinity to but not within the granular osmiophilic material. These results strongly suggest that CADASIL mutations specifically impair the clearance of the Notch3 ectodomain, but not the cytosolic domain, from the cell surface.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 03:33:33