RRC ID 46449
Author Stavoe AK, Colón-Ramos DA.
Title Netrin instructs synaptic vesicle clustering through Rac GTPase, MIG-10, and the actin cytoskeleton.
Journal J Cell Biol
Abstract Netrin is a chemotrophic factor known to regulate a number of neurodevelopmental processes, including cell migration, axon guidance, and synaptogenesis. Although the role of Netrin in synaptogenesis is conserved throughout evolution, the mechanisms by which it instructs synapse assembly are not understood. Here we identify a mechanism by which the Netrin receptor UNC-40/DCC instructs synaptic vesicle clustering in vivo. UNC-40 localized to presynaptic regions in response to Netrin. We show that UNC-40 interacted with CED-5/DOCK180 and instructed CED-5 presynaptic localization. CED-5 in turn signaled through CED-10/Rac1 and MIG-10/Lamellipodin to organize the actin cytoskeleton in presynaptic regions. Localization of this signaling pathway to presynaptic regions was necessary for synaptic vesicle clustering during synapse assembly but not for the subcellular localization of active zone proteins. Thus, vesicle clustering and localization of active zone proteins are instructed by separate pathways downstream of Netrin. Our data indicate that signaling modules known to organize the actin cytoskeleton during guidance can be co-opted to instruct synaptic vesicle clustering.
Volume 197(1)
Pages 75-88
Published 2012-4-2
DOI 10.1083/jcb.201110127
PII jcb.201110127
PMID 22451697
PMC PMC3317799
MeSH Actin Cytoskeleton / metabolism* Animals Caenorhabditis elegans / cytology* Caenorhabditis elegans / enzymology Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Nerve Tissue Proteins / metabolism* Netrins Synaptic Vesicles / metabolism* rac GTP-Binding Proteins / metabolism*
IF 8.811
Times Cited 41
C.elegans tm1949 tm1950