title: MIG-10 functions with ABI-1 to mediate the UNC-6 and SLT-1 axon guidance signaling pathways.
abstract: Extracellular guidance cues steer axons towards their targets by eliciting morphological changes in the growth cone. A key part of this process is the asymmetric recruitment of the cytoplasmic scaffolding protein MIG-10 (lamellipodin). MIG-10 is thought to asymmetrically promote outgrowth by inducing actin polymerization. However, the mechanism that links MIG-10 to actin polymerization is not known. We have identified the actin regulatory protein ABI-1 as a partner for MIG-10 that can mediate its outgrowth-promoting activity. The SH3 domain of ABI-1 binds to MIG-10, and loss of function of either of these proteins causes similar axon guidance defects. Like MIG-10, ABI-1 functions in both the attractive UNC-6 (netrin) pathway and the repulsive SLT-1 (slit) pathway. Dosage sensitive genetic interactions indicate that MIG-10 functions with ABI-1 and WVE-1 to mediate axon guidance. Epistasis analysis reveals that ABI-1 and WVE-1 function downstream of MIG-10 to mediate its outgrowth-promoting activity. Moreover, experiments with cultured mammalian cells suggest that the interaction between MIG-10 and ABI-1 mediates a conserved mechanism that promotes formation of lamellipodia. Together, these observations suggest that MIG-10 interacts with ABI-1 and WVE-1 to mediate the UNC-6 and SLT-1 guidance pathways.
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Quinn
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000075385:Netrins; D055495:Neurogenesis; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; C105812:Mig-10 protein, C elegans; D009419:Nerve Tissue Proteins; D000075385:Netrins; C078146:UNC-6 protein, C elegans; C539886:abi-1 protein, C elegans; C492285:slt-1 protein, C elegans; C532811:wve-1 protein, C elegans