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First published online 18 October 2006
doi: 10.1242/dev.02648

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

¹ Center for Neuroscience, and Cell and Developmental Biology Graduate Group, University of California, Davis, CA 95616, USA.
² Section of Neurobiology, Physiology and Behavior, College of Biological Sciences, and Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, CA 95616, USA.
³ Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RR, UK.
⁴ Department of Psychiatry and Behavioral Sciences, University of California, Sacramento, CA 95817, USA.

^* Author for correspondence (e-mail: hjcheng{at}ucdavis.edu)

Accepted 15 September 2006

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.

Key words: Axon guidance, Netrin, unc-73, rac, P21-activated kinase

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