RRC ID 51513
Author Borgen MA, Wang D, Grill B.
Title RPM-1 regulates axon termination by affecting growth cone collapse and microtubule stability.
Journal Development
Abstract 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.
Volume 144(24)
Pages 4658-4672
Published 2017-12-15
DOI 10.1242/dev.154187
PII dev.154187
PMID 29084805
PMC PMC5769622
MeSH Acetyltransferases / metabolism Actin Cytoskeleton / metabolism Animals Animals, Genetically Modified Axons / physiology* Caenorhabditis elegans / embryology* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Growth Cones / physiology* Guanine Nucleotide Exchange Factors / genetics* Microtubule-Associated Proteins / metabolism Microtubules / physiology* Nerve Growth Factors / metabolism Nerve Tissue Proteins / metabolism Signal Transduction rac GTP-Binding Proteins / metabolism rho GTP-Binding Proteins / metabolism
IF 5.611
Times Cited 8
Resource
C.elegans tm5597 tm597