TY - JOUR
T1 - SRPK2 phosphorylates tau and mediates the cognitive defects in Alzheimer's disease
AU - Hong, Yi
AU - Chan, Chi Bun
AU - Kwon, Il Sun
AU - Li, Xuekun
AU - Song, Mingke
AU - Lee, Hyun Pil
AU - Liu, Xia
AU - Sompol, Pradoldej
AU - Jin, Peng
AU - Lee, Hyoung Gon
AU - Yu, Shan Ping
AU - Ye, Keqiang
PY - 2012/11/28
Y1 - 2012/11/28
N2 - Serine-arginine protein kinases 2 (SRPK2) is a cell cycle-regulated kinase that phosphorylates serine/arginine domain-containing proteins and mediates pre-mRNA splicing with unclear function in neurons. Here, we show that SRPK2 phosphorylates tau on S214, suppresses tau-dependent microtubule polymerization, and inhibits axonal elongationin neurons. DepletionofSRPK2in dentate gyrus inhibits tau phosphorylation in APP/PS1 mouse and alleviates the impaired cognitive behaviors. The defective LTP in APP/PS1 mice is also improved after SRPK2 depletion. Moreover, active SRPK2isincreasedinthe cortexof APP/PS1 mice and the pathological structures of human Alzheimer's disease (AD) brain. Therefore, our study suggestsSRPK2may contributetothe formationofhyperphosphorylated tau and the pathogenesis of AD.
AB - Serine-arginine protein kinases 2 (SRPK2) is a cell cycle-regulated kinase that phosphorylates serine/arginine domain-containing proteins and mediates pre-mRNA splicing with unclear function in neurons. Here, we show that SRPK2 phosphorylates tau on S214, suppresses tau-dependent microtubule polymerization, and inhibits axonal elongationin neurons. DepletionofSRPK2in dentate gyrus inhibits tau phosphorylation in APP/PS1 mouse and alleviates the impaired cognitive behaviors. The defective LTP in APP/PS1 mice is also improved after SRPK2 depletion. Moreover, active SRPK2isincreasedinthe cortexof APP/PS1 mice and the pathological structures of human Alzheimer's disease (AD) brain. Therefore, our study suggestsSRPK2may contributetothe formationofhyperphosphorylated tau and the pathogenesis of AD.
UR - http://www.scopus.com/inward/record.url?scp=84870228676&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870228676&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.3300-12.2012
DO - 10.1523/JNEUROSCI.3300-12.2012
M3 - Article
C2 - 23197718
AN - SCOPUS:84870228676
SN - 0270-6474
VL - 32
SP - 17262
EP - 17272
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 48
ER -
