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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'Protein tyrosine phosphatase δ mediates the sema3a-induced cortical basal dendritic arborization through the activation of fyn tyrosine kinase'. Together they form a unique fingerprint.

Cite this