The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in Caenorhabditis elegans
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2018-06-01
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| Series: | G3: Genes, Genomes, Genetics |
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| Online Access: | http://g3journal.org/lookup/doi/10.1534/g3.118.200148 |
| _version_ | 1818571641198739456 |
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| author | Jamie K. Alan Sara K. Robinson Katie L. Magsig Rafael S. Demarco Erik A. Lundquist |
| author_facet | Jamie K. Alan Sara K. Robinson Katie L. Magsig Rafael S. Demarco Erik A. Lundquist |
| author_sort | Jamie K. Alan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T13:58:43Z |
| format | Article |
| id | doaj.art-9530b415d6f14566a9d5248ca6614c83 |
| institution | Directory Open Access Journal |
| issn | 2160-1836 |
| language | English |
| last_indexed | 2024-12-14T13:58:43Z |
| publishDate | 2018-06-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | G3: Genes, Genomes, Genetics |
| spelling | doaj.art-9530b415d6f14566a9d5248ca6614c832022-12-21T22:58:46ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362018-06-01861885189510.1534/g3.118.2001484The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in Caenorhabditis elegansJamie K. AlanSara K. RobinsonKatie L. MagsigRafael S. DemarcoErik A. LundquistDuring 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.http://g3journal.org/lookup/doi/10.1534/g3.118.200148CHW-1SAX-3/Roboaxon pathfindingCRP-1CDC-42 |
| spellingShingle | Jamie K. Alan Sara K. Robinson Katie L. Magsig Rafael S. Demarco Erik A. Lundquist The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in Caenorhabditis elegans G3: Genes, Genomes, Genetics CHW-1 SAX-3/Robo axon pathfinding CRP-1 CDC-42 |
| title | The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in Caenorhabditis elegans |
| title_full | The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in Caenorhabditis elegans |
| title_fullStr | The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in Caenorhabditis elegans |
| title_full_unstemmed | The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in Caenorhabditis elegans |
| title_short | The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in Caenorhabditis elegans |
| title_sort | atypical rho gtpase chw 1 works with sax 3 robo to mediate axon guidance in caenorhabditis elegans |
| topic | CHW-1 SAX-3/Robo axon pathfinding CRP-1 CDC-42 |
| url | http://g3journal.org/lookup/doi/10.1534/g3.118.200148 |
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