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

Abstract

<p class="first" id="d4083114e141">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 <i>in vivo</i>. Using the mechanosensory neurons of <i>C. elegans</i>, 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 <i>in vivo</i>, and suggest that RPM-1 signaling destabilizes microtubules to facilitate growth cone collapse and axon termination. </p><p class="first" id="d4083114e154"> <b>Summary:</b> <i>In vivo</i> analysis of <i>C. elegans</i> mechanosensory neurons indicates that the signaling hub RPM-1 regulates growth cone collapse, and is inhibited by PTL-1/Tau. </p>