The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in Caenorhabditis elegans.
Abstract — Entities Highlighted
Gene/ProteinChemicalDiseasePhenotypeAnatomyDev. Stage
During development, neuronal cells extend an axon toward their target destination in response to a cue to form a properly functioning nervous system. Rho proteins, Ras-related small GTPases that regulate cytoskeletal organization and dynamics, cell adhesion, and motility, are known to regulate axon guidance. Despite extensive knowledge about canonical Rho proteins (RhoA/Rac1/Cdc42), little is known about the Caenorhabditis elegans (C. elegans) atypical Cdc42-like family members CHW-1 and CRP-1 in regards to axon pathfinding and neuronal migration. chw-1(Chp/Wrch) encodes a protein that resembles human Chp (Wrch-2/RhoV) and Wrch-1 (RhoU), and crp-1 encodes for a protein that resembles TC10 and TCL. Here, we show that chw-1 works redundantly with crp-1 and cdc-42 in axon guidance. Furthermore, proper levels of chw-1 expression and activity are required for proper axon guidance. When examining CHW-1 GTPase mutants, we found that the native CHW-1 protein is likely partially activated, and mutations at a conserved residue (position 12 using Ras numbering, position 18 in CHW-1) alter axon guidance and neural migration. Additionally, we showed that chw-1 genetically interacts with the guidance receptor sax-3 in PDE neurons. Finally, in VD/DD motor neurons, chw-1 works downstream of sax-3 to control axon guidance. In summary, this is the first study implicating the atypical Rho GTPases chw-1 and crp-1 in axon guidance. Furthermore, this is the first evidence of genetic interaction between chw-1 and the guidance receptor sax-3 These data suggest that chw-1 is likely acting downstream and/or in parallel to sax-3 in axon guidance.
Relation Network
Specialists Used
gene_gene: 14
All Extracted Relations (18)
| Entity 1 | Relation | Entity 2 | Confidence | Specialist | Direction |
|---|---|---|---|---|---|
| chw-1 | regulation | sax-3 | 100% | gene_gene | supports |
| chw-1 | regulation | sax-3 | 100% | gene_gene | supports |
| crp-1 | regulation | cdc-42 | 100% | gene_gene | supports |
| chw-1 | regulation | chw-1 | 100% | gene_gene | supports |
| CHW-1 | regulation | Chp | 100% | gene_gene | supports |
| chw-1 | regulation | crp-1 | 100% | gene_gene | supports |
| CHW-1 | regulation | CHW-1 | 100% | gene_gene | supports |
| CHW-1 | regulation | CRP-1 | 100% | gene_gene | supports |
| chw-1 | regulation | crp-1 | 99% | gene_gene | supports |
| CRP-1 | regulation | crp-1 | 99% | gene_gene | supports |
| CHW-1 | regulation | chw-1 | 98% | gene_gene | supports |
| Rac1 | regulation | Chp | 97% | gene_gene | supports |
| chw-1 | regulation | sax-3 | 96% | gene_gene | supports |
| Rac1 | regulation | CHW-1 | 88% | gene_gene | supports |
| chw-1 | downstream of | sax-3 | 59% | — | uncertain |
| chw-1 | interacts with | sax-3 | 59% | — | supports |
| CHW-1 | positively regulates | CHW-1 | 56% | — | uncertain |
| small | regulates | organ | 52% | — | supports |