title: SRPK2 phosphorylates tau and mediates the cognitive defects in Alzheimer's disease.
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 elongation in neurons. Depletion of SRPK2 in 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 SRPK2 is increased in the cortex of APP/PS1 mice and the pathological structures of human Alzheimer's disease (AD) brain. Therefore, our study suggests SRPK2 may contribute to the formation of hyperphosphorylated tau and the pathogenesis of AD.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hong
authors.forename: Chi Bun
authors.initials: CB
authors.lastname: Chan
authors.forename: Il-Sun
authors.initials: IS
authors.lastname: Kwon
authors.forename: Xuekun
authors.initials: X
authors.lastname: Li
authors.forename: Mingke
authors.initials: M
authors.lastname: Song
authors.forename: Hyun-Pil
authors.initials: HP
authors.lastname: Lee
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Pradoldej
authors.initials: P
authors.lastname: Sompol
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Hyoung-gon
authors.initials: HG
authors.lastname: Lee
authors.forename: Shan Ping
authors.initials: SP
authors.lastname: Yu
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D016875:tau Proteins; C484679:Srpk2 protein, mouse; D017346:Protein Serine-Threonine Kinases