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Titolo:
Multiple effects of aspartate mutant presenilin 1 on the processing and trafficking of amyloid precursor protein
Autore:
Kim, SH; Leem, JY; Lah, JJ; Slunt, HH; Levey, AI; Thinakaran, G; Sisodia, SS;
Indirizzi:
Univ Chicago, Dept Neurobiol Pharmacol & Physiol, Chicago, IL 60637 USA Univ Chicago Chicago IL USA 60637 rmacol & Physiol, Chicago, IL 60637 USA Emory Univ, Dept Neurol, Atlanta, GA 30322 USA Emory Univ Atlanta GA USA 30322 Univ, Dept Neurol, Atlanta, GA 30322 USA Johns Hopkins Univ, Neuropathol Lab, Baltimore, MD 21205 USA Johns HopkinsUniv Baltimore MD USA 21205 ol Lab, Baltimore, MD 21205 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 46, volume: 276, anno: 2001,
pagine: 43343 - 43350
SICI:
0021-9258(20011116)276:46<43343:MEOAMP>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-SECRETASE ACTIVITY; DISEASE-ASSOCIATED PRESENILIN-1; FAMILIAL ALZHEIMERS-DISEASE; BETA-PROTEIN; SUBCELLULAR-LOCALIZATION; ENDOGENOUS PRESENILIN-1; IN-VIVO; TRANSMEMBRANE ASPARTATES; INTRACELLULAR DOMAIN; TRANSFECTED CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
72
Recensione:
Indirizzi per estratti:
Indirizzo: Sisodia, SS Univ Chicago, Dept Neurobiol Pharmacol & Physiol, Abbott 510,947 E 58th St, Chicago, IL 60637 USA Univ Chicago Abbott 510,947 E 58th St Chicago IL USA 60637 USA
Citazione:
S.H. Kim et al., "Multiple effects of aspartate mutant presenilin 1 on the processing and trafficking of amyloid precursor protein", J BIOL CHEM, 276(46), 2001, pp. 43343-43350

Abstract

PS1 deficiency and expression of PS1 with substitutions of two conserved transmembrane aspartate residues ("PS1 aspartate variants") leads to the reduction of A beta peptide secretion and the accumulation of amyloid precursor protein (APP) C-terminal fragments. To define the nature of the "dominantnegative" effect of the PS1 aspartate variants, we stably expressed PS1 harboring aspartate to alanine substitutions at codons 257 (D257A) or 385 (D385A), singly or in combination (D257A/ D385A), in mouse neuroblastoma, N2a cells. Expression of the PS1 aspartate variants resulted in marked accumulation of intracellular and cell surface APP C-terminal fragments. While expression of the D385A PS1 variant reduced the levels of secreted AP peptides,we now show that neither the PS1 D257A nor D257A/D385A variants impair A beta production. Surprisingly, the stability of both immature and mature forms of APP is dramatically elevated in cells expressing PS1 aspartate variants, commensurate with an increase in the cell surface levels of APP. These findings lead us to conclude that the stability and trafficking of APP can be profoundly modulated by coexpression of PS1 with mutations at aspartate 257 and aspartate 385.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 13:56:33