The Caenorhabditis elegans P21-activated kinases are differentially required for UNC-6/netrin-mediated commissural motor axon guidance.
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.
Lucanic
Mark
M
Center for Neuroscience, and Cell and Developmental Biology Graduate Group, University of California, Davis, CA 95616, USA.
Kiley
Maureen
M
Ashcroft
Neville
N
L'etoile
Noelle
N
Cheng
Hwai-Jong
HJ
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology*; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017931:DNA Primers; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000075385:Netrins; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000378:metabolism
C407268:CED-10 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D000075385:Netrins; C078146:UNC-6 protein, C elegans; D011494:Protein Kinases; C101878:pak-1 protein, C elegans; C517554:Max-2 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; C442327:Mig-2 protein, C elegans; D020744:rac GTP-Binding Proteins