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 Genetics
Rafael S DemarcoErik A Lundquist

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...Continue Reading

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Citations

Mar 19, 2014·Cell Death and Differentiation·L J NeukommM O Hengartner
Oct 4, 2013·Small GTPases·Jamie K Alan, Erik A Lundquist
Jun 18, 2014·Small GTPases·Mirela Spillane, Gianluca Gallo
Aug 21, 2013·PloS One·Nithya SubramanianSubramanian Krishnakumar
Jun 9, 2016·Proceedings of the National Academy of Sciences of the United States of America·Chaogu ZhengMartin Chalfie
Mar 8, 2017·Molecular and Cellular Neurosciences·Omotola F OmotadeJames Q Zheng
Apr 15, 2018·G3 : Genes - Genomes - Genetics·Jamie K AlanErik A Lundquist
Jan 24, 2017·Genetics·Andrew D ChisholmWilliam G Wadsworth
Dec 15, 2015·Molecular Neurobiology·Yan Xu, Christopher C Quinn
Aug 16, 2018·Frontiers in Cellular Neuroscience·Nicholas P Boyer, Stephanie L Gupton
Dec 19, 2018·International Journal of Molecular Sciences·Hendrik SchönebornRolf Heumann
Feb 26, 2015·The Journal of Biological Chemistry·Tao WangDale D Tang
Oct 30, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Beatriz Sáenz-NarcisoJuan Cabello
May 16, 2021·Developmental Biology·Jacob I MardickDavid J Reiner

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Datasets Mentioned

BETA
ADY42014

Methods Mentioned

BETA
GTPases
GTPase
myristoylation
transgenic
PCR
GTP
Fluorescence microscopy
transfection
Assay

Software Mentioned

ImageJ
ClustalW
BLAST
BLASTP

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