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- W2155655690 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." @default.
- W2155655690 created "2016-06-24" @default.
- W2155655690 creator A5014643816 @default.
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- W2155655690 creator A5044769115 @default.
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- W2155655690 creator A5067680334 @default.
- W2155655690 date "2012-10-01" @default.
- W2155655690 modified "2023-09-26" @default.
- W2155655690 title "Synaptic vesicle clustering requires a distinct MIG-10/Lamellipodin isoform and ABI-1 downstream from Netrin" @default.
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- W2155655690 doi "https://doi.org/10.1101/gad.193409.112" @default.
- W2155655690 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3465741" @default.
- W2155655690 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23028145" @default.
- W2155655690 hasPublicationYear "2012" @default.
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