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dc.contributor.authorGujar, Mahekta R.
dc.contributor.authorStricker, Aubrie M.
dc.contributor.authorLundquist, Erik A.
dc.identifier.citationGujar, 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.
dc.descriptionThis work is licensed under a Creative Commons Attribution 4.0 International License.en_US
dc.description.abstractUNC-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.sponsorshipNIH R01NS040945en_US
dc.description.sponsorshipNIH R56NS095682en_US
dc.description.sponsorshipNIH P20GM103638en_US
dc.description.sponsorshipNIH Office of Research Infrastructure Programs (P40 OD010440)en_US
dc.description.sponsorshipNIH GM103418en_US
dc.description.sponsorshipUniversity of Kansas Center for Undergraduate Researchen_US
dc.publisherPublic Library of Scienceen_US
dc.rights© 2019 Gujar et al.en_US
dc.titleRHO-1 and the Rho GEF RHGF-1 interact with UNC-6/Netrin signaling to regulate growth cone protrusion and microtubule organization in Caenorhabditis elegansen_US
kusw.kuauthorGujar, Mahekta R.
kusw.kuauthorStricker, Aubrie M.
kusw.kuauthorLundquist, Erik A.
kusw.kudepartmentMolecular Biosciencesen_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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© 2019 Gujar et al.
Except where otherwise noted, this item's license is described as: © 2019 Gujar et al.