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Titolo:
Subcellular compartment and molecular subdomain of beta-amyloid precursor protein relevant to the A beta 42-promoting effects of Alzheimer mutant presenilin 2
Autore:
Iwata, H; Tomita, T; Maruyama, K; Iwatsubo, T;
Indirizzi:
Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Neuropathol & Neurosci, Bunkyo Ku, Tokyo 1130033, Japan Univ Tokyo Tokyo Japan 1130033 Neurosci, Bunkyo Ku, Tokyo 1130033, Japan Saitama Med Sch, Dept Pharmacol, Moroyama, Saitama 3500495, Japan Saitama Med Sch Moroyama Saitama Japan 3500495 ma, Saitama 3500495, Japan
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 24, volume: 276, anno: 2001,
pagine: 21678 - 21685
SICI:
0021-9258(20010615)276:24<21678:SCAMSO>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-SECRETASE INHIBITORS; ENDOPLASMIC-RETICULUM; PATHOGENIC MUTATION; DISEASE INCREASE; DISTINCT SITES; APP GENE; CLEAVAGE; PEPTIDES; CELLS; GENERATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Iwatsubo, T Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Neuropathol & Neurosci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan Univ Tokyo 7-3-1 Hongo Tokyo Japan 1130033 kyo 1130033, Japan
Citazione:
H. Iwata et al., "Subcellular compartment and molecular subdomain of beta-amyloid precursor protein relevant to the A beta 42-promoting effects of Alzheimer mutant presenilin 2", J BIOL CHEM, 276(24), 2001, pp. 21678-21685

Abstract

Increased production of amyloid beta peptides ending at position 42 (A beta 42) is one of the pathogenic phenotypes caused by mutant forms of presenilins (PS) linked to familial Alzheimer's disease. To identify the subcellular compartment(s) in which familial Alzheimer's disease mutant PS2 (mt PS2)affects the gamma -cleavage of beta APP to increase A beta 42, we co-expressed the C-terminal 99-amino acid fragment of beta APP (C100) tagged with sorting signals to the endoplasmic reticulum (C100/ER) or to the trans-Golginetwork (C100/TGN) together with mt PS2 in N2a cells. C100/TGN co-transfected with mt PS2 increased levels or ratios of intracellular as well as secreted A beta 42 at similar levels to those with C100 without signals (C100/WT), whereas C100/ER yielded a negligible level of A beta, which was not affected by co-transfection of mt PS2, To identify the molecular subdomain of beta APP required for the effects of mt PS2, we next co-expressed C100 variously truncated at the C-terminal cytoplasmic domain together with mt PS2, All types of C-terminally truncated C100 variants including that lacking the entire cytoplasmic domain yielded the secreted form of A beta at levels comparable with those from C100/WT, and cotransfection of mt PS2 increased the secretion of A beta 42, These results suggest that (i) late intracellular compartments including TGN are the major sites in which A beta 42 is produced and up-regulated by mt PS2 and that (ii) the anterior half of C100 lacking the entire cytoplasmic domain is sufficient for the overproduction of A beta 42 caused by mt PS2.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 23:33:33