dc.contributor.author | Gujar, Mahekta R. | |
dc.contributor.author | Stricker, Aubrie M. | |
dc.contributor.author | Lundquist, Erik A. | |
dc.date.accessioned | 2020-11-18T15:55:06Z | |
dc.date.available | 2020-11-18T15:55:06Z | |
dc.date.issued | 2019-06-24 | |
dc.identifier.citation | Gujar, M. R., Stricker, A. M., & Lundquist, E. A. (2019). RHO-1 and the Rho GEF RHGF-1 interact with UNC-6/Netrin signaling to regulate growth cone protrusion and microtubule organization in Caenorhabditis elegans. PLoS genetics, 15(6), e1007960. https://doi.org/10.1371/journal.pgen.1007960 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/30875 | |
dc.description | This work is licensed under a Creative Commons Attribution 4.0 International License. | en_US |
dc.description.abstract | UNC-6/Netrin is a conserved axon guidance cue that directs growth cone migrations in the dorsal-ventral axis of C. elegans and in the vertebrate spinal cord. UNC-6/Netrin is expressed in ventral cells, and growth cones migrate ventrally toward or dorsally away from UNC-6/Netrin. Recent studies of growth cone behavior during outgrowth in vivo in C. elegans have led to a polarity/protrusion model in directed growth cone migration away from UNC-6/Netrin. In this model, UNC-6/Netrin first polarizes the growth cone via the UNC-5 receptor, leading to dorsally biased protrusion and F-actin accumulation. UNC-6/Netrin then regulates protrusion based on this polarity. The receptor UNC-40/DCC drives protrusion dorsally, away from the UNC-6/Netrin source, and the UNC-5 receptor inhibits protrusion ventrally, near the UNC-6/Netrin source, resulting in dorsal migration. UNC-5 inhibits protrusion in part by excluding microtubules from the growth cone, which are pro-protrusive. Here we report that the RHO-1/RhoA GTPase and its activator GEF RHGF-1 inhibit growth cone protrusion and MT accumulation in growth cones, similar to UNC-5. However, growth cone polarity of protrusion and F-actin were unaffected by RHO-1 and RHGF-1. Thus, RHO-1 signaling acts specifically as a negative regulator of protrusion and MT accumulation, and not polarity. Genetic interactions are consistent with RHO-1 and RHGF-1 acting with UNC-5, as well as with a parallel pathway, to regulate protrusion. The cytoskeletal interacting molecule UNC-33/CRMP was required for RHO-1 activity to inhibit MT accumulation, suggesting that UNC-33/CRMP might act downstream of RHO-1. In sum, these studies describe a new role of RHO-1 and RHGF-1 in regulation of growth cone protrusion by UNC-6/Netrin. | en_US |
dc.description.sponsorship | NIH R01NS040945 | en_US |
dc.description.sponsorship | NIH R56NS095682 | en_US |
dc.description.sponsorship | NIH P20GM103638 | en_US |
dc.description.sponsorship | NIH Office of Research Infrastructure Programs (P40 OD010440) | en_US |
dc.description.sponsorship | NIH GM103418 | en_US |
dc.description.sponsorship | University of Kansas Center for Undergraduate Research | en_US |
dc.publisher | Public Library of Science | en_US |
dc.rights | © 2019 Gujar et al. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.title | RHO-1 and the Rho GEF RHGF-1 interact with UNC-6/Netrin signaling to regulate growth cone protrusion and microtubule organization in Caenorhabditis elegans | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Gujar, Mahekta R. | |
kusw.kuauthor | Stricker, Aubrie M. | |
kusw.kuauthor | Lundquist, Erik A. | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.1371/journal.pgen.1007960 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-8509-600X | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-6819-4815 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC6611649 | en_US |
dc.rights.accessrights | openAccess | en_US |