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	Protein Tyrosine Phosphatase δ Mediates the Sema3A-Induced Cortical Basal Dendritic Arborization through the Activation of Fyn Tyrosine Kinase.
掲載誌名	正式名：Journal of Neuroscience 略　 称：J Neurosci ISSNコード：02706474/15292401
掲載区分	国外
巻・号・頁	37(30),pp.7125-7139
著者・共著者	Nakamura F†*, Okada T, Shishikura M, Uetani N, Taniguchi M, Yagi T, Iwakura Y, Ohshima T, Goshima Y, Strittmatter SM*.
担当区分	筆頭著者,責任著者
発行年月	2017/07
概要	Leukocyte common antigen-related (LAR) class protein tyrosine phosphatases (PTPs) are critical for axonal guidance; however, their relation to specific guidance cues is poorly defined. We here show that PTP-3, a LAR homolog in Caenorhabditis elegans, is involved in axon guidance regulated by Semaphorin-2A-signaling. PTPδ, one of the vertebrate LAR class PTPs, participates in the Semaphorin-3A (Sema3A)-induced growth cone collapse response of primary cultured dorsal root ganglion neurons from Mus musculus embryos. In vivo, however, the contribution of PTPδ in Sema3A-regualted axon guidance was minimal. Instead, PTPδ played a major role in Sema3A-dependent cortical dendritic growth. Ptpδ-/- and Sema3a-/- mutant mice exhibited poor arborization of basal dendrites of cortical layer V neurons. This phenotype was observed in both male and female mutants. The double-heterozygous mutants, Ptpδ+/-; Sema3a+/-, also showed a similar phenotype, indicating the genetic interaction. In Ptpδ-/- brains, Fyn and Src kinases were hyperphosphorylated at their C-terminal Tyr527 residues. Sema3A-stimulation induced dephosphorylation of Tyr527 in the dendrites of wild-type cortical neurons but not of Ptpδ-/- Arborization of cortical basal dendrites was reduced in Fyn-/- as well as in Ptpδ+/-; Fyn+/- double-heterozygous mutants. Collectively, PTPδ mediates Sema3A-signaling through the activation of Fyn by C-terminal dephosphorylation.
DOI	10.1523/JNEUROSCI.2519-16.2017.