SRPK2 phosphorylates tau and mediates the cognitive defects in Alzheimer's disease

Yi Hong, Chi Bun Chan, Il Sun Kwon, Xuekun Li, Mingke Song, Hyun Pil Lee, Xia Liu, Pradoldej Sompol, Peng Jin, Hyoung Gon Lee, Shan Ping Yu, Keqiang Ye

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)17262-17272
Number of pages11
JournalJournal of Neuroscience
Volume32
Issue number48
DOIs
StatePublished - Nov 28 2012

ASJC Scopus subject areas

  • Neuroscience (all)

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