title: Different effects of Alzheimer-associated mutations of presenilin 1 on its processing.
abstract: Presenilin 1 (PS 1) shows missense mutations in most early-onset familial Alzheimer's disease (FAD). Transfection of cDNA for wild type PS 1 into rat pheochromocytoma PC12 cells generated a 47 kDa full-size PS 1 protein, which was processed into a 28 kDa N-terminal fragment and a 19 kDa C-terminal fragment. We prepared selected Alzheimer-associated mutations (Gly384Ala, Leu392Val, and Cys410Tyr) of PS 1, which localized after a possible cleavage site. By transient expression in PC12 cells and rat glioma cell line, C6, we examined their influence on the processing of PS 1. Cys410Tyr inhibited proteolytic processing of PS 1, while Gly384Ala and Leu392Val did not. Thus, the Alzheimer related mutations can be divided into two groups in terms of their effect on the proteolytic cleavage of PS 1.
authors.affiliation: Mitsubishi Kasei Institute of Life Sciences, Machida-shi, Tokyo, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Murayama
authors.forename: T
authors.initials: T
authors.lastname: Honda
authors.forename: M
authors.initials: M
authors.lastname: Mercken
authors.forename: M
authors.initials: M
authors.lastname: Murayama
authors.forename: K
authors.initials: K
authors.lastname: Yasutake
authors.forename: N
authors.initials: N
authors.lastname: Nihonmatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Nakazato
authors.forename: G
authors.initials: G
authors.lastname: Michel
authors.forename: S
authors.initials: S
authors.lastname: Song
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: A
authors.initials: A
authors.lastname: Takashima
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D016716:PC12 Cells; D017354:Point Mutation; D053764:Presenilin-1; D011499:Protein Processing, Post-Translational; D051381:Rats; D014162:Transfection
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1