RRC ID 46450
Author Stavoe AK, Nelson JC, Martínez-Velázquez LA, Klein M, Samuel AD, Colón-Ramos DA.
Title Synaptic vesicle clustering requires a distinct MIG-10/Lamellipodin isoform and ABI-1 downstream from Netrin.
Journal Genes Dev
Abstract The chemotrophic factor Netrin can simultaneously instruct different neurodevelopmental programs in individual neurons in vivo. How neurons correctly interpret the Netrin signal and undergo the appropriate neurodevelopmental response is not understood. Here we identify MIG-10 isoforms as critical determinants of individual cellular responses to Netrin. We determined that distinct MIG-10 isoforms, varying only in their N-terminal motifs, can localize to specific subcellular domains and are differentially required for discrete neurodevelopmental processes in vivo. We identified MIG-10B as an isoform uniquely capable of localizing to presynaptic regions and instructing synaptic vesicle clustering in response to Netrin. MIG-10B interacts with Abl-interacting protein-1 (ABI-1)/Abi1, a component of the WAVE complex, to organize the actin cytoskeleton at presynaptic sites and instruct vesicle clustering through SNN-1/Synapsin. We identified a motif in the MIG-10B N-terminal domain that is required for its function and localization to presynaptic sites. With this motif, we engineered a dominant-negative MIG-10B construct that disrupts vesicle clustering and animal thermotaxis behavior when expressed in a single neuron in vivo. Our findings indicate that the unique N-terminal domains confer distinct MIG-10 isoforms with unique capabilities to localize to distinct subcellular compartments, organize the actin cytoskeleton at these sites, and instruct distinct Netrin-dependent neurodevelopmental programs.
Volume 26(19)
Pages 2206-21
Published 2012-10-1
DOI 10.1101/gad.193409.112
PII 26/19/2206
PMID 23028145
PMC PMC3465741
MeSH Actin Cytoskeleton / metabolism Animals Behavior, Animal / physiology Caenorhabditis elegans / embryology* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Cell Movement Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism* Gene Expression Profiling Interneurons / cytology Motor Neurons / cytology Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism Netrins Protein Isoforms Protein Transport / genetics Synaptic Vesicles / genetics Synaptic Vesicles / metabolism*
IF 9.527
Times Cited 25
C.elegans tm494 tm2557