RRC ID 59392
Author Nørgaard S, Deng S, Cao W, Pocock R.
Title Distinct CED-10/Rac1 domains confer context-specific functions in development.
Journal PLoS Genet
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.
Volume 14(9)
Pages e1007670
Published 2018-9-1
DOI 10.1371/journal.pgen.1007670
PII PGENETICS-D-18-01418
PMID 30265669
PMC PMC6179291
MeSH Animals Animals, Genetically Modified Axons / physiology Caenorhabditis elegans / growth & development* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Female Glutamic Acid / genetics Glycine / genetics Male Microfilament Proteins / metabolism* Mutagenesis Nerve Tissue Proteins / metabolism* Neuronal Outgrowth / genetics* Protein Domains / genetics Protein Domains / physiology* rac GTP-Binding Proteins / genetics* rac GTP-Binding Proteins / metabolism
IF 5.224
Times Cited 1
Resource
C.elegans tm597 tm1949 tm6234 tm403