title: Altered localization of amyloid precursor protein under endoplasmic reticulum stress.
abstract: Recent reports have shown that the endoplasmic reticulum (ER) stress is relevant to the pathogenesis of Alzheimer disease. Following the amyloid cascade hypothesis, we therefore attempted to investigate the effects of ER stress on amyloid-beta peptide (Abeta) generation. In this study, we found that ER stress altered the localization of amyloid precursor protein (APP) from late compartments to early compartments of the secretory pathway, and decreased the level of Abeta 40 and Abeta 42 release by beta- and gamma-cutting. Transient transfection with BiP/GRP78 also caused a shift of APP and a reduction in Abeta secretion. It was revealed that the ER stress response facilitated binding of BiP/GRP78 to APP, thereby causing it to be retained in the early compartments apart from a location suitable for the cleavages of Abeta. These findings suggest that induction of BiP/GRP78 during ER stress may be one of the regulatory mechanisms of Abeta generation.
authors.affiliation: Division of Psychiatry, Course of Internal Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. kudo@psy.med.osaka-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Masayo
authors.initials: M
authors.lastname: Okumura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
authors.forename: Wataru
authors.initials: W
authors.lastname: Araki
authors.forename: Takashi
authors.initials: T
authors.lastname: Morihara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tanimukai
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Kamagata
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Tabuchi
authors.forename: Ryo
authors.initials: R
authors.lastname: Kimura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kanayama
authors.forename: Akio
authors.initials: A
authors.lastname: Fukumori
authors.forename: Shinji
authors.initials: S
authors.lastname: Tagami
authors.forename: Masayasu
authors.initials: M
authors.lastname: Okochi
authors.forename: Mikiko
authors.initials: M
authors.lastname: Kubo
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tanii
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tabira
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human