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Titolo:
Increased generation of alternatively cleaved beta-amyloid peptides in cells expressing mutants of the amyloid precursor protein defective in endocytosis
Autore:
Cescato, R; Dumermuth, E; Spiess, M; Paganetti, PA;
Indirizzi:
Novartis Pharma AG, CH-4002 Basel, Switzerland Novartis Pharma AG Basel Switzerland CH-4002 CH-4002 Basel, Switzerland Univ Basel, Biozentrum, Basel, Switzerland Univ Basel Basel SwitzerlandUniv Basel, Biozentrum, Basel, Switzerland
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 3, volume: 74, anno: 2000,
pagine: 1131 - 1139
SICI:
0022-3042(200003)74:3<1131:IGOACB>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALZHEIMERS-DISEASE; SECRETASE CLEAVAGE; SIGNAL SEQUENCE; SENILE PLAQUES; CORE PROTEIN; IDENTIFICATION; RECEPTOR; PATHWAY; SITES; LOCALIZATION;
Keywords:
protein processing; proteolysis; beta-amyloid precursor protein; endocytosis; HEK 293 cells; beta-secretase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Paganetti, PA Novartis Pharma AG, POB WSJ 386-8-28, CH-4002 Basel, Switzerland Novartis Pharma AG POB WSJ 386-8-28 Basel Switzerland CH-4002
Citazione:
R. Cescato et al., "Increased generation of alternatively cleaved beta-amyloid peptides in cells expressing mutants of the amyloid precursor protein defective in endocytosis", J NEUROCHEM, 74(3), 2000, pp. 1131-1139

Abstract

The subcellular location of the secretases processing the beta-amyloid precursor protein (APP) is not established yet. We analyzed the generation of the beta-amyloid peptide (A beta) in human embryonic kidney 293 cell lines stably expressing wild-type and noninternalizing mutants of human APP, APP lacking the entire cytoplasmic domain or with both tyrosine residues of themotif GYENPTY mutated to alanine showed at least fivefold reduced endocytosis. In these cell lines, the production of A beta(1-40) was substantially reduced, but accompanied by the appearance of two prominent alternative A beta peptides differing at the amino-termini. Based on antibody reactivity and mobility in high-resolution gels in comparison with defined A beta fragments, these peptides were identified as A beta(3-40) and A beta(5-40). Notably, these alternalive A beta peptides were not generated when the APP mutants were retained in the early secretory pathway by treatment with brefeldin A. These results indicate that the alternative processing is the result of APP accumulation at the plasma membrane and provide evidence of distinct beta-secretase activities. Cleavage amino-terminal to position 1 of A beta occurs predominantly in endosomes, whereas the processing at positions 3 or5 takes place at the plasma membrane.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 21:46:41