Open AccessPresenilin 1 associates with glycogen synthase kinase-3β and its substrate tau
Author(s) -
Akihiko Takashima,
Miyuki Murayama,
Ohoshi Murayama,
Toshiyuki Kohno,
Toshiyuki Honda,
Kaori Yasutake,
Naomi Nihonmatsu,
Marc Mercken,
Hideyo Yamaguchi,
Shiro Sugihara,
Benjamin Wolozin
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.16.9637
Subject(s) - gsk 3 , presenilin , glycogen synthase , phosphorylation , kinase , gsk3b , tau protein , mutant , microtubule , biology , microbiology and biotechnology , biochemistry , chemistry , alzheimer's disease , gene , disease , medicine
Families bearing mutations in the presenilin 1 (PS1) gene develop Alzheimer’s disease. Previous studies have shown that the Alzheimer-associated mutations in PS1 increase production of amyloid β protein (Aβ1–42 ). We now show that PS1 also regulates phosphorylation of the microtubule-associated protein tau. PS1 directly binds tau and a tau kinase, glycogen synthase kinase 3β (GSK-3β). Deletion studies show that both tau and GSK-3β bind to the same region of PS1, residues 250–298, whereas the binding domain on tau is the microtubule-binding repeat region. The ability of PS1 to bring tau and GSK-3β into close proximity suggests that PS1 may regulate the interaction of tau with GSK-3β. Mutations in PS1 that cause Alzheimer’s disease increase the ability of PS1 to bind GSK-3β and, correspondingly, increase its tau-directed kinase activity. We propose that the increased association of GSK-3β with mutant PS1 leads to increased phosphorylation of tau.