MIG-10 Functions with ABI-1 to Mediate the UNC-6 and SLT-1 Axon Guidance Signaling Pathways

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. © 2012 xu,quinn.