The Caenorhabditis elegans P21-activated kinases are differentially required for UNC-6/netrin-mediated commissural motor axon guidance

Mark Lucanic, Maureen Kiley, Neville Ashcroft, Noelle L'Etoile, Hwai-Jong Cheng

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

P21 activated kinases (PAKs) are major downstream effectors of rac-related small GTPases that regulate various cellular processes. We have identified the new PAK gene max-2 in a screen for mutants disrupted in UNC-6/netrin-mediated commissural axon guidance. There are three Caenorhabditis elegans PAKs. We find that each C. elegans PAK represents a distinct group previously$identified in other species. Here we examine their roles in the postembryonic migration of the P cell neuroblasts and the axon guidance of the ventral cord commissural motoneurons (VCCMNs). We find that the two PAKs, max-2 and pak-1, are redundantly required for P cell migration and function with UNC-73/Trio and the rac GTPases (CED-10 and MIG-2). During axon guidance of the VCCMNs, PAK-1 also acts with the rac GTPases, CED-10 and MIG-2, and is completely redundant with MAX-2. Interestingly, we find that unlike MAX-2 activity during P cell migration, for motoneuron axon guidance max-2 is also required in parallel to this PAK-1 pathway, independent of rac GTPase signaling. Finally, we provide evidence that MAX-2 functions downstream of the UNC-6/netrin receptor UNC-5 during axon repulsion and is an integral part of its signaling.

Original languageEnglish (US)
Pages (from-to)4549-4559
Number of pages11
JournalDevelopment
Volume133
Issue number22
DOIs
StatePublished - Nov 2006

Keywords

  • Axon guidance
  • Netrin
  • P21-activated kinase
  • Rac
  • Unc-73

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

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