RPM-1 regulates axon termination by affecting growth cone collapse and microtubule stability.

Axon termination is essential for efficient and accurate nervous system construction. At present, relatively little is known about how growth cone collapse occurs prior to axon termination in vivo Using the mechanosensory neurons of C. elegans , we found collapse prior to axon termination is protracted, with the growth cone transitioning from a dynamic to a static state. Growth cone collapse prior to termination is facilitated by the signaling hub RPM-1. Given the prominence of the cytoskeleton in growth cone collapse, we assessed the relationship between RPM-1 and regulators of actin dynamics and microtubule stability. Our results reveal several important findings about how axon termination is orchestrated: (1) RPM-1 functions in parallel to RHO-1 and CRMP/UNC-33, but is suppressed by the Rac isoform MIG-2; (2) RPM-1 opposes the function of microtubule stabilizers, including tubulin acetyltransferases; and (3) genetic epistasis suggests the microtubule-stabilizing protein Tau/PTL-1 potentially inhibits RPM-1. These findings provide insight into how growth cone collapse is regulated during axon termination in vivo , and suggest that RPM-1 signaling destabilizes microtubules to facilitate growth cone collapse and axon termination.