title: Sequestration of sorcin by aberrant forms of tau results in the defective calcium homeostasis.
abstract: Neurofi brillary tangles (NFTs) of microtubule-associated protein tau are a pathological hallmark of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress has been known to be involved in the pathogenesis of AD. However, the exact role of ER stress in tau pathology has not yet been clearly elucidated. In present study, the possible relationship between tau pathology and ER stress was examined in terms of sorcin, which is a calcium binding protein and plays an important role in calcium homeostasis. Our previous yeast two hybrid study showed that sorcin is a novel tau interacting protein. Caspase-3-cleaved tau (T4C3) showed significantly increased tau-sorcin interaction compared to wild type tau (T4). Thapsigargin-induced ER stress and co-expression of constitutively active GSK3β (GSK3β-S9A) also exhibited significantly increased tau-sorcin interactions. T4C3-expressing cells showed potentiated thapsigargin-induced apoptosis and disruption of intracellular calcium homeostasis compared to T4-expressing cells. Overexpression of sorcin signifi cantly attenuated thapsigargin-induced apoptosis and disruption of calcium homeostasis. In contrary, siRNA-mediated knock-down of sorcin showed significantly increased thapsigargin-induced apoptosis and disruption of calcium homeostasis. These data strongly suggest that sequestration of sorcin by aberrant forms of tau compromises the function of sorcin, such as calcium homeostasis and cellular resistance by ER stress, which may consequently result in the contribution to the progression of AD.
authors.affiliation: Department of Pharmacology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Song-In
authors.initials: SI
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Wanjoo
authors.initials: W
authors.lastname: Chun
keywords: Alzheimer's disease; Endoplasmic reticulum stress; Sorcin; Tau; Thapsigargin