Distinct CED-10/Rac1 domains confer context-specific functions in development

Steffen Norgaard, Shuer Deng, Wei Cao, Roger Pocock

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

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.
Original languageEnglish
Article numbere1007670
Number of pages24
JournalPLoS Genetics
Volume14
Issue number9
DOIs
Publication statusPublished - 28 Sep 2018

Keywords

  • guanosine triphosphatase
  • axons
  • axon guidance
  • caenorhabditis elegans
  • apoptosis
  • statistical data
  • allelles
  • neurons

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