2020 Fiscal Year Annual Research Report
Understanding how the JNK MAPK pathway regulates axon regeneration
| Project/Area Number |
19K16911
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | axon regeneration / C. elegans / MAPK / CDK14 / Wnt / CDC-42 / EPHX-1 |
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| Outline of Annual Research Achievements |
Our previous analysis of one of the potential regulators of the MAPK pathway, the C. elegans CDK14 homolog cdk-14, indicated that it is involved in regulation of axon regeneration, but the mechanism was unknown. We discovered that CDK-14 acts via the myosin phosphorylation pathway in a kinase-independent manner by regulating the non-canonical branch of the conserved Wnt signaling pathway. In particular, CDK-14 binds to the Dishevelled homolog MIG-5 and acts in the EGL-20/Wnt-MIG-1/Fz Wnt signaling pathway. We showed furthermore that CDK-14 interacts with and activates the RhoGEF EPHX-1, which in turn activates the small GTPase CDC-42 to induce the activation of myosin II via inactivation of myosin phosphatase and thereby promote axon regeneration.
The large degree of conservation of the non-canonical Wnt pathway and CDK14 between C. elegans and humans suggests that CDK14 may function in similar way to control axon regeneration in humans.
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