The gene
mig-10 is necessary for the long range anteroposterior migration during embryogenesis of the neurons CAN, ALM, and HSN. Mutations in
mig-10 result in incomplete migrations of all three neurons. Since ALM and CAN migrate posteriorly and HSN migrates anteriorly,
mig-10 mutations are believed to affect the basic mechanism of migration rather than affecting positional information. Mutations in
mig-10 also affect axon guidance of several neurons, including the CAN, HSN, AVM, PVM, and ADL neurons, and overexpression of MIG-10 promotes axon outgrowth in vivo. Like its vertebrate homologs lamellipodin and RIAM, MIG-10 binds to an Ena/VASP protein (UNC-34); Ena/VASP proteins are involved in regulating actin dynamics. Overexpression of MIG-10 or its vertebrate homologs in cultured cells causes lamellipodia formation. Several lines of evidence suggest that MIG-10 might interact with members of the Ras GTPase family. MIG-10 contains a Ras-association (RA) domain as well as a pleckstrin homology (PH) domain. A similar RAPH domain in RIAM is known to interact with Rap1, a member of the Ras GTPase family. In addition, double mutants of
mig-10 with either of two C. elegans rac genes,
mig-2 or
ced-10, show an enhanced migration defect, suggesting an interaction between
mig-10 and the rac genes. We are testing the hypothesis that MIG-10 interacts with one or more of the members of the Ras GTPase family to transduce environmental signals, ultimately resulting in oriented neuronal migration or axon outgrowth. We are currently using a yeast two-hybrid system to investigate potential interactions between Ras-family proteins and MIG-10. Our initial results suggest that the MIG-10 RAPH domain on its own does not interact with any of the Ras family members tested. We plan to test the full length MIG-10 protein for interactions with the Ras family, as well as screening the entire C. elegans cDNA library for other potential MIG-10 interactors.