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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2206-2221 |
| Number of pages | 16 |
| Journal | Genes and Development |
| Volume | 26 |
| Issue number | 19 |
| DOIs | |
| State | Published - Oct 1 2012 |
| Externally published | Yes |
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Keywords
- ABI-1/ABI1
- C. elegans
- MIG-10/lamellipodin
- Netrin
- Synaptic vesicle clustering
- Thermotaxis
ASJC Scopus subject areas
- Genetics
- Developmental Biology
Cite this
Synaptic vesicle clustering requires a distinct MIG-10/lamellipodin isoform and ABI-1 downstream from Netrin. / Stavoe, Andrea K H; Nelson, Jessica C.; Martínez-Velázquez, Luis A.; Klein, Mason; Samuel, Aravinthan D T; Colón-Ramos, Daniel A.
In: Genes and Development, Vol. 26, No. 19, 01.10.2012, p. 2206-2221.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synaptic vesicle clustering requires a distinct MIG-10/lamellipodin isoform and ABI-1 downstream from Netrin
AU - Stavoe, Andrea K H
AU - Nelson, Jessica C.
AU - Martínez-Velázquez, Luis A.
AU - Klein, Mason
AU - Samuel, Aravinthan D T
AU - Colón-Ramos, Daniel A.
PY - 2012/10/1
Y1 - 2012/10/1
N2 - 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.
AB - 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.
KW - ABI-1/ABI1
KW - C. elegans
KW - MIG-10/lamellipodin
KW - Netrin
KW - Synaptic vesicle clustering
KW - Thermotaxis
UR - http://www.scopus.com/inward/record.url?scp=84867149086&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867149086&partnerID=8YFLogxK
U2 - 10.1101/gad.193409.112
DO - 10.1101/gad.193409.112
M3 - Article
C2 - 23028145
AN - SCOPUS:84867149086
VL - 26
SP - 2206
EP - 2221
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 19
ER -