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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.oanotesPer Sherpa Romeo 11/18/2020:

PLoS Genetics [Open panel below]Publication Information TitlePLoS Genetics [English] ISSNs Print: 1553-7390 Electronic: 1553-7404 URL PublishersPublic Library of Science [Commercial Publisher] DOAJ Listing Requires APCYes [Data provided by DOAJ] [Close panel below]Publisher Policy Open Access pathways permitted by this journal's policy are listed below by article version. Click on a pathway for a more detailed view.

Published Version NoneCC BYPMC Any Website, Journal Website, +1 OA PublishingThis pathway includes Open Access publishing EmbargoNo Embargo LicenceCC BY 4.0 Copyright OwnerAuthors Publisher DepositPubMed Central Location Any Website Named Repository (PubMed Central) Journal Website ConditionsPublished source must be acknowledged with citation
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.