1. Different effects of Alzheimer-associated mutations of presenilin 1 on its processing
- Author
-
Ohoshi Murayama, Toshiyuki Honda, Akihiko Takashima, Naomi Nihonmatsu, Gilles Michel, Miyuki Murayama, Kazuki Sato, Kaori Yasutake, Hiroshi Takahashi, Yuko Nakazato, Shaochuen Song, and Marc Mercken
- Subjects
medicine.medical_specialty ,Blotting, Western ,Biology ,Transfection ,Cleavage (embryo) ,PC12 Cells ,Presenilin ,Alzheimer Disease ,Complementary DNA ,Internal medicine ,Presenilin-1 ,medicine ,Animals ,Humans ,Point Mutation ,Missense mutation ,General Neuroscience ,Wild type ,Membrane Proteins ,Molecular biology ,In vitro ,Rats ,Endocrinology ,Cell culture ,Protein Processing, Post-Translational - 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.
- Published
- 1997
- Full Text
- View/download PDF