イシヅカ ユウタ   Yuta Ishizuka
  石塚 佑太
   所属   川崎医科大学  医学部 基礎医学 病態代謝学
   職種   講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Nuclear Translocation of Calcium/Calmodulin-dependent Protein Kinase IIδ3 Promoted by Protein Phosphatase-1 Enhances Brain-derived Neurotrophic Factor Expression in Dopaminergic Neurons.
掲載誌名 正式名:The Journal of biological chemistry
略  称:J Biol Chem
ISSNコード:1083351X/00219258
掲載区分国外
出版社 ScienceDirect
巻・号・頁 290(35),21663-75頁
著者・共著者 Norifumi Shioda, Masahiro Sawai, Yuta Ishizuka, Tomoaki Shirao, Kohji Fukunaga
発行年月 2015/08
概要 We have reported previously that dopamine D2 receptor stimulation activates calcium/calmodulin-dependent protein kinase II (CaMKII) δ3, a CaMKII nuclear isoform, increasing BDNF gene expression. However, the mechanisms underlying that activity remained unclear. Here we report that CaMKIIδ3 is dephosphorylated at Ser(332) by protein phosphatase 1 (PP1), promoting CaMKIIδ3 nuclear translocation. Neuro-2a cells transfected with CaMKIIδ3 showed cytoplasmic and nuclear staining, but the staining was predominantly nuclear when CaMKIIδ3 was coexpressed with PP1. Indeed, PP1 and CaMKIIδ3 coexpression significantly increased nuclear CaMKII activity and enhanced BDNF expression. In support of this idea, chronic administration of the dopamine D2 receptor partial agonist aripiprazole increased PP1 activity and promoted nuclear CaMKIIδ3 translocation and BDNF expression in the rat brain substantia nigra. Moreover, aripiprazole treatment enhanced neurite extension and inhibited cell death in cultured dopaminergic neurons, effects blocked by PP1γ knockdown. Taken together, nuclear translocation of CaMKIIδ3 following dephosphorylation at Ser(332) by PP1 likely accounts for BDNF expression and subsequent neurite extension and survival of dopaminergic neurons.
DOI 10.1074/jbc.M115.664920
PMID 26163515