Document Detail


Synaptic vesicle clustering requires a distinct MIG-10/Lamellipodin isoform and ABI-1 downstream from Netrin.
MedLine Citation:
PMID:  23028145     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Andrea K H Stavoe; Jessica C Nelson; Luis A Martínez-Velázquez; Mason Klein; Aravinthan D T Samuel; Daniel A Colón-Ramos
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Genes & development     Volume:  26     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2012-12-05     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2206-21     Citation Subset:  IM    
Affiliation:
Program in Cellular Neuroscience, Neurodegeneration, and Repair, Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
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MeSH Terms
Descriptor/Qualifier:
Actin Cytoskeleton / metabolism
Animals
Behavior, Animal / physiology
Caenorhabditis elegans / embryology*,  metabolism
Caenorhabditis elegans Proteins / genetics*,  metabolism*
Cell Movement
Cytoskeletal Proteins / genetics,  metabolism*
Gene Expression Profiling
Interneurons / cytology
Motor Neurons / cytology
Nerve Tissue Proteins / genetics*,  metabolism
Protein Isoforms
Protein Transport / genetics
Synaptic Vesicles / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
R00 NS057931/NS/NINDS NIH HHS; T32-GM007223/GM/NIGMS NIH HHS; T32-NS41228/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Caenorhabditis elegans Proteins; 0/Cytoskeletal Proteins; 0/Mig-10 protein, C elegans; 0/Nerve Tissue Proteins; 0/Protein Isoforms; 0/UNC-6 protein, C elegans; 0/abi-1 protein, C elegans
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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