RRC ID 46308
著者 Demarco RS, Struckhoff EC, Lundquist EA.
タイトル The Rac GTP exchange factor TIAM-1 acts with CDC-42 and the guidance receptor UNC-40/DCC in neuronal protrusion and axon guidance.
ジャーナル PLoS Genet
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.
巻・号 8(4)
ページ e1002665
公開日 2012-1-1
DOI 10.1371/journal.pgen.1002665
PII PGENETICS-D-11-01581
PMID 22570618
PMC PMC3343084
MeSH Animals Axons / metabolism Caenorhabditis elegans* / genetics Caenorhabditis elegans* / growth & development Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Adhesion Molecules / genetics Cell Adhesion Molecules / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* GTP-Binding Proteins / genetics GTP-Binding Proteins / metabolism* Growth Cones / metabolism Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism* Nerve Tissue Proteins / metabolism Neurons / metabolism Pseudopodia / genetics Pseudopodia / physiology Signal Transduction T-Lymphoma Invasion and Metastasis-inducing Protein 1 rac GTP-Binding Proteins* / genetics rac GTP-Binding Proteins* / metabolism
IF 5.175
引用数 36
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm1556 tm597