The Rac GTP Exchange Factor TIAM-1 Acts with CDC-42 and the Guidance Receptor UNC-40/DCC in Neuronal Protrusion and Axon Guidance
dc.contributor.author | Demarco, Rafael Senos | |
dc.contributor.author | Struckhoff, Eric Charles | |
dc.contributor.author | Lundquist, Erik A. | |
dc.date.accessioned | 2014-03-18T16:47:27Z | |
dc.date.available | 2014-03-18T16:47:27Z | |
dc.date.issued | 2012-04-26 | |
dc.identifier.citation | Demarco, R. S., Struckhoff, E. C., & Lundquist, E. A. (2012). The Rac GTP Exchange Factor TIAM-1 Acts with CDC-42 and the Guidance Receptor UNC-40/DCC in Neuronal Protrusion and Axon Guidance. PLoS Genet, 8(4). http://dx.doi.org/10.1371/journal.pgen.1002665 | |
dc.identifier.uri | http://hdl.handle.net/1808/13227 | |
dc.description.abstract | The mechanisms linking guidance receptors to cytoskeletal dynamics in the growth cone during axon extension remain mysterious. The Rho-family GTPases Rac and CDC-42 are key regulators of growth cone lamellipodia and filopodia formation, yet little is understood about how these molecules interact in growth cone outgrowth or how the activities of these molecules are regulated in distinct contexts. UNC-73/Trio is a well-characterized Rac GTP exchange factor in Caenorhabditis elegans axon pathfinding, yet UNC-73 does not control CED-10/Rac downstream of UNC-6/Netrin in attractive axon guidance. Here we show that C. elegans TIAM-1 is a Rac-specific GEF that links CDC-42 and Rac signaling in lamellipodia and filopodia formation downstream of UNC-40/DCC. We also show that TIAM-1 acts with UNC-40/DCC in axon guidance. Our results indicate that a CDC-42/TIAM-1/Rac GTPase signaling pathway drives lamellipodia and filopodia formation downstream of the UNC-40/DCC guidance receptor, a novel set of interactions between these molecules. Furthermore, we show that TIAM-1 acts with UNC-40/DCC in axon guidance, suggesting that TIAM-1 might regulate growth cone protrusion via Rac GTPases in response to UNC-40/DCC. Our results also suggest that Rac GTPase activity is controlled by different GEFs in distinct axon guidance contexts, explaining how Rac GTPases can specifically control multiple cellular functions. | |
dc.description.sponsorship | This work was supported by NIH grant R01 NS40945 to EAL and NIH grant P20 RR016475 from the INBRE/IDEA Program of the National Center for Research Resources (J. Hunt, P.I.). The Caenorhabditis Genetics Center is funded by the NIH National Center for Research Resources (NCRR). | |
dc.publisher | Public Library of Science | |
dc.rights | ©2012 Demarco et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Axon guidance | |
dc.subject | Axon guidance receptors | |
dc.subject | Axons | |
dc.subject | Caenorhabditis elegans | |
dc.subject | Complementary DNA | |
dc.subject | Mutation | |
dc.subject | Neurons | |
dc.subject | Partial differential equations | |
dc.title | The Rac GTP Exchange Factor TIAM-1 Acts with CDC-42 and the Guidance Receptor UNC-40/DCC in Neuronal Protrusion and Axon Guidance | |
dc.type | Article | |
kusw.kuauthor | Demarco, Rafael S. | |
kusw.kuauthor | Struckhoff, Eric C. | |
kusw.kuauthor | Lundquist, Erik A. | |
kusw.kudepartment | Molecular Biosciences | |
kusw.oastatus | fullparticipation | |
dc.identifier.doi | 10.1371/journal.pgen.1002665 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item meets KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess |
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Except where otherwise noted, this item's license is described as: ©2012 Demarco et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.