The Mechanism Of The Transmembrane Protein MIG-13 In Regulating C.Elegans Q Neuroblast Migration

Directional cell migration has essential functions in development,immunity,and cancer.Transmembrane protein Lrp12/Mig12 a has been reported to be required for normal cortical neuronal migration,but no any mechanisms have emerged so far.Using the Caenorhabditis elegans Q neuroblast as our experimental system,we find that a non-receptor tyrosine kinase SRC-1 interacts with and phosphorylates MIG-13/Lrp12 intracellular tail,phosphorylated MIG-13/Lrp12 is linked to the Arp2/3 complex through ABL-1-WAVE and SEM-5-WASP two paralell pathways,and activates branched actin polymerization at the leading edge.Meanwhile,WAVE and WASP are largely organized into separate clusters at the leading edge,and the amount of WASP is less than WAVE but could be elevated by WAVE mutations.Furthermore,our candidate gene screens isolate a receptor-like tyrosine phosphatase PTP-3,which is specifically enriched in the lateral and rear,antagonizes MIG-13/Lrp12-SRC-1 siganling axis.These findings provide a cell-intrinsic mechanism of MIG-13/Lrp12 controls directional neuroblast migration.