Protein tyrosine phosphatase δ mediates the sema3a-induced cortical basal dendritic arborization through the activation of fyn tyrosine kinase

Fumio Nakamura, Takako Okada, Maria Shishikura, Noriko Uetani, Masahiko Taniguchi, Takeshi Yagi, Yoichiro Iwakura, Toshio Ohshima, Yoshio Goshima, Stephen M. Strittmatter

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    Abstract

    Leukocytecommonantigen-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 growthconecollapseresponseofprimarycultured dorsal rootganglionneuronsfromMusmusculusembryos.Invivo,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 layerVneurons. This phenotype was observed in both male and female mutants. The double-heterozygous mutants, Ptpδ-/-; Sema3a-/-, also showed a similar phenotype, indicating the geneticinteraction.InPtpδ-/-brains, Fynand Srckinaseswerehyper phosphorylatedat theirC-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.

    Original languageEnglish
    Pages (from-to)7125-7139
    Number of pages15
    JournalJournal of Neuroscience
    Volume37
    Issue number30
    DOIs
    Publication statusPublished - 2017 Jul 26

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    Keywords

    • C. elegans
    • Dendritic growth
    • Fyn
    • LAR
    • PTP-3
    • PTPRD
    • PTPδ
    • Pyramidal neuron
    • Sema2A
    • Sema3A

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Nakamura, F., Okada, T., Shishikura, M., Uetani, N., Taniguchi, M., Yagi, T., Iwakura, Y., Ohshima, T., Goshima, Y., & Strittmatter, S. M. (2017). Protein tyrosine phosphatase δ mediates the sema3a-induced cortical basal dendritic arborization through the activation of fyn tyrosine kinase. Journal of Neuroscience, 37(30), 7125-7139. https://doi.org/10.1523/JNEUROSCI.2519-16.2017