ナカムラ　フミオ   Nakamura Fumio   中村　史雄    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Proteome and behavioral alterations in phosphorylation-deficient mutant Collapsin Response Mediator Protein2 knock-in mice.
掲載誌名	正式名：Neurochemistry international 略　 称：Neurochem Int ISSNコード：(1872-9754)0197-0186(Linking)
掲載区分	国外
巻・号・頁	119,pp.207-217
著者・共著者	Nakamura Haruko†, Takahashi-Jitsuki Aoi, Makihara Hiroko, Asano Tetsuya, Kimura Yayoi, Nakabayashi Jun, Yamashita Naoya, Kawamoto Yuko, Nakamura Fumio, Ohshima Toshio, Hirano Hisashi, Tanaka Fumiaki, Goshima Yoshio*
発行年月	2018/10
概要	CRMP2 was identified as an intracellular molecule mediating the signaling of the axon guidance molecule Sema3A. In Sema3A signaling, Cdk5 primarily phosphorylates CRMP2 at Ser522. GSK-3β subsequently phosphorylates the residues of Thr509 and Thr514. In Alzheimer's disease, hyper-phosphorylated forms of CRMP2 are accumulated in the paired helical filaments. We previously created CRMP2 S522A knock-in (crmp2ki/ki) mice and demonstrated that the phosphorylation of CRMP2 at Ser522 is involved in normal dendrite patterning in cortical neurons. However, the behavioral impact and in vivo signaling network of the CRMP2 phosphorylation are not fully understood. In this study, we performed behavioral and proteomics analysis of crmp2ki/ki mice. The crmp2ki/ki mice appeared healthy and showed no obvious differences in physical characteristics compared to wild-type mice, but they showed impaired emotional behavior, reduced sociality, and low sensitivity to pain stimulation. Through mass-spectrometry-based proteomic analysis, we found that 59 proteins were increased and 77 proteins were decreased in the prefrontal cortex of crmp2ki/ki mice. Notably, CRMP3, CRMP4, and CRMP5, the other CRMP family proteins, were increased in crmp2ki/ki mice. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses identified 14 pathways in increased total proteins and 13 pathways in decreased total proteins which are associated with the pathogenesis of Parkinson's, Alzheimer's, and Huntington's diseases. We also detected 20 pathways in increased phosphopeptides and 16 pathways in decreased phosphopeptides including "inflammatory mediator regulation of TRP channels" in crmp2ki/ki mice. Our study suggests that the phosphorylation of CRMP2 at Ser522 is involved in the signaling pathways that may be related to neuropsychiatric and neurodegenerative diseases and pain.
DOI	10.1016/j.neuint.2018.04.009
PMID	29758318