Protein Tyrosine Phosphatase δ Mediates the Sema3A-Induced Cortical Basal Dendritic Arborization through the Activation of Fyn Tyrosine Kinase
| Autor: | Toshio Ohshima, Maria Shishikura, Stephen M. Strittmatter, Takeshi Yagi, Fumio Nakamura, Masahiko Taniguchi, Yoshio Goshima, Takako Okada, Noriko Uetani, Yoichiro Iwakura |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Mice Transgenic Protein tyrosine phosphatase Proto-Oncogene Proteins c-fyn Gene Expression Regulation Enzymologic Mice 03 medical and health sciences FYN Semaphorin Animals Research Articles Cells Cultured Caenorhabditis elegans Cerebral Cortex Mice Knockout Neuronal Plasticity biology Kinase General Neuroscience Receptor-Like Protein Tyrosine Phosphatases Class 2 Semaphorin-3A SEMA3A Dendrites Protein-Tyrosine Kinases biology.organism_classification Cell biology Enzyme Activation Mice Inbred C57BL 030104 developmental biology Female Axon guidance Neuroscience Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | The Journal of Neuroscience. 37:7125-7139 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2519-16.2017 |
| Popis: | 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. SIGNIFICANCE STATEMENT The relation of leukocyte common antigen-related (LAR) class protein tyrosine phosphatases (PTPs) and specific axon guidance cues is poorly defined. We show that PTP-3, a LAR homolog in Caenorhabditis elegans, participates in Sema2A-regulated axon guidance. PTPδ, a member of vertebrate LAR class PTPs, is involved in Sema3A-regulated cortical dendritic growth. In Sema3A signaling, PTPδ activates Fyn and Src kinases by dephosphorylating their C-terminal Tyr residues. This is the first evidence showing that LAR class PTPs participate in Semaphorin signaling in vivo. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|