C. elegans vab-6 encodes a KIF3A kinesin and functions cell non-autonomously to regulate epidermal morphogenesis.

Cells undergo strict regulation to develop their shape in a process called morphogenesis. Caenorhabditis elegans with mutations in the variable abnormal (vab) class of genes have been shown to display epidermal and neuronal morphological defects. While several vab genes have been well-characterized, the function of the vab-6 gene remains unknown. Here, we show that vab-6 is synonymous with a subunit of the kinesin-II heterotrimeric motor complex called klp-20/Kif3a, a motor well-understood to be involved in developing sensory cilia in the nervous system. We show that certain klp-20 alleles cause animals to develop a bumpy body phenotype that is variable but most severe in mutants containing single amino-acid substitutions in the catalytic head-domain sites of the protein. Surprisingly, animals carrying a klp-20 null allele do not show the bumpy epidermal phenotype suggesting genetic redundancy and only when mutant versions of the KLP-20 protein are present, the epidermal phenotype is observed. The bumpy epidermal phenotype was not observed in other kinesin-2 mutants, suggesting that KLP-20 is functioning independently from its role in intraflagellar transport (IFT) during ciliogenesis. Interestingly, despite having such a prominent epidermal phenotype, KLP-20 is not expressed in the epidermis, strongly suggesting a cell non-autonomous role in which it regulates epidermal morphogenesis.

The Caenorhabditis elegans Eph receptor activates NCK and N-WASP, and inhibits Ena/VASP to regulate growth cone dynamics during axon guidance.

The Eph receptor tyrosine kinases (RTKs) are regulators of cell migration and axon guidance. However, our understanding of the molecular mechanisms by which Eph RTKs regulate these processes is still incomplete. To understand how Eph receptors regulate axon guidance in Caenorhabditis elegans, we screened for suppressors of axon guidance defects caused by a hyperactive VAB-1/Eph RTK. We identified NCK-1 and WSP-1/N-WASP as downstream effectors of VAB-1. Furthermore, VAB-1, NCK-1, and WSP-1 can form a complex in vitro. We also report that NCK-1 can physically bind UNC-34/Enabled (Ena), and suggest that VAB-1 inhibits the NCK-1/UNC-34 complex and negatively regulates UNC-34. Our results provide a model of the molecular events that allow the VAB-1 RTK to regulate actin dynamics for axon guidance. We suggest that VAB-1/Eph RTK can stop axonal outgrowth by inhibiting filopodia formation at the growth cone by activating Arp2/3 through a VAB-1/NCK-1/WSP-1 complex and by inhibiting UNC-34/Ena activity.

The VAB-1 Eph receptor tyrosine kinase and SAX-3/Robo neuronal receptors function together during C. elegans embryonic morphogenesis.

Mutations that affect the single C. elegans Eph receptor tyrosine kinase VAB-1 cause defects in cell movements during embryogenesis. Here, we provide genetic and molecular evidence that the VAB-1 Eph receptor functions with another neuronal receptor, SAX-3/Robo, for proper embryogenesis. Our analysis of sax-3 mutants shows that SAX-3/Robo functions with the VAB-1 Eph receptor for gastrulation cleft closure and ventral epidermal enclosure. In addition, SAX-3 functions autonomously for epidermal morphogenesis independently of VAB-1. A double-mutant combination between vab-1 and slt-1 unmasks a role for the SLT-1 ligand in embryogenesis. We provide evidence for a physical interaction between the VAB-1 tyrosine kinase domain and the juxtamembrane and CC1 region of the SAX-3/Robo receptor. Gene dosage, non-allelic non-complementation experiments and co-localization of the two receptors are consistent with a model in which these two receptors form a complex and function together during embryogenesis.