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bioRxiv · 10.1101/341412

Distinct CED-10/Rac1 Domains Confer Context-Specific Functions in Neuronal Development

Pocock, R.·Noergaard, S.·Deng, S.·Cao, W.
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Abstract

Rac GTPases act as master switches to coordinate multiple interweaved signaling pathways. A major function for Rac GTPases is to control neurite development by influencing downstream effector molecules and pathways. In Caenorhabditis elegans, the Rac proteins CED-10, RAC-2 and MIG-2 act in parallel to control axon outgrowth and guidance. Here, we have identified a single glycine residue in the CED-10/Rac1 Switch 1 region that confers a non-redundant function in axon outgrowth but not guidance. Mutation of this glycine to glutamic acid (G30E) reduces GTP binding and inhibits axon outgrowth but does not affect other canonical CED-10 functions. This demonstrates previously unappreciated domain-specific functions within the CED-10 protein. Further, we reveal that when CED-10 function is diminished, the adaptor protein NAB-1 (Neurabin) and its interacting partner SYD-1 (Rho-GAP-like protein) can act as inhibitors of axon outgrowth. Together, we reveal that specific domains and residues within Rac GTPases can confer context-dependent functions during animal development.

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Pocock, R., Noergaard, S., Deng, S., Cao, W.. 2018-06-08. Distinct CED-10/Rac1 Domains Confer Context-Specific Functions in Neuronal Development. https://doi.org/10.1101/341412

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