Historical Background
Human Trio was identified in the late 1990s in a two-hybrid screen using the cytoplasmic fragment of the transmembrane tyrosine phosphatase LAR as a bait (Debant et al. 1996). The name of Trio came from the observation that Trio comprises three enzymatic domains: two GEF domains predicted to activate Rho GTPases and one serine kinase domain. It was rapidly shown that both GEF domains are active, the GEFD1 activating Rac1/RhoG and the GEFD2 domain acting on RhoA. While the function of Trio was unclear at that time, the first indication of its function came from studies in C. elegans, when it was discovered that UNC-73, a major regulator of axon guidance and cell motility, was the ortholog of mammalian Trio (Steven et al. 1998). Two years later, the Drosophila trio gene was shown by different groups to be essential for axon guidance viathe activation of Rac through its first GEF domain (Bateman and Van...
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ba W, Yan Y, Reijnders MR, Schuurs-Hoeijmakers JH, Feenstra I, Bongers EM, Bosch DG, De Leeuw N, Pfundt R, Gilissen C, De Vries PF, Veltman JA, Hoischen A, Mefford HC, Eichler EE, Vissers LE, Nadif Kasri N, De Vries BB. TRIO loss of function is associated with mild intellectual disability and affects dendritic branching and synapse function. Hum Mol Genet. 2016;25:892–902.
Bateman J, Van Vactor D. The Trio family of guanine-nucleotide-exchange factors: regulators of axon guidance. J Cell Sci. 2001;114:1973–80.
Briancon-Marjollet A, Ghogha A, Nawabi H, Triki I, Auziol C, Fromont S, Piche C, Enslen H, Chebli K, Cloutier JF, Castellani V, Debant A, Lamarche-Vane N. Trio mediates netrin-1-induced Rac1 activation in axon outgrowth and guidance. Mol Cell Biol. 2008;28:2314–23.
Cannet A, Schmidt S, Delaval B, Debant A. Identification of a mitotic Rac-GEF, Trio, that counteracts MgcRacGAP function during cytokinesis. Mol Biol Cell. 2014;25:4063–71.
Charrasse S, Comunale F, Fortier M, Portales-Casamar E, Debant A, Gauthier-Rouviere C. M-cadherin activates Rac1 GTPase through the Rho-GEF trio during myoblast fusion. Mol Biol Cell. 2007;18:1734–43.
De Rubeis S, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014;515:209–15.
Debant A, Serra-Pages C, Seipel K, O’Brien S, Tang M, Park SH, Streuli M. The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac- specific and rho-specific guanine nucleotide exchange factor domains. Proc Natl Acad Sci USA. 1996;93:5466–71.
Degeer J, Boudeau J, Schmidt S, Bedford F, Lamarche-Vane N, Debant A. Tyrosine phosphorylation of the Rho guanine nucleotide exchange factor Trio regulates netrin-1/DCC-mediated cortical axon outgrowth. Mol Cell Biol. 2013;33:739–51.
Degeer J, Kaplan A, Mattar P, Morabito M, Stochaj U, Kennedy TE, Debant A, Cayouette M, Fournier AE, Lamarche-Vane N. Hsc70 chaperone activity underlies Trio GEF function in axon growth and guidance induced by netrin-1. J Cell Biol. 2015;210:817–32.
Delespaul L, Lesluyes T, Perot G, Brulard C, Lartigue L, Baud J, Lagarde P, Le Guellec S, Neuville A, Terrier P, Vince-Ranchere D, Schmidt S, Debant A, Coindre JM, Chibon F. Recurrent TRIO fusion in nontranslocation-related sarcomas. Clin Cancer Res. 2017;23:857–67.
Estrach S, Schmidt S, Diriong S, Penna A, Blangy A, Fort P, Debant A. The human Rho-GEF trio and its target GTPase RhoG are involved in the NGF pathway, leading to neurite outgrowth. Curr Biol. 2002;12:307–12.
Herring BE, Nicoll RA. Kalirin and Trio proteins serve critical roles in excitatory synaptic transmission and LTP. Proc Natl Acad Sci U S A. 2016;113:2264–9.
Kashef J, Kohler A, Kuriyama S, Alfandari D, Mayor R, Wedlich D. Cadherin-11 regulates protrusive activity in Xenopus cranial neural crest cells upstream of Trio and the small GTPases. Genes Dev. 2009;23:1393–8.
Moshfegh Y, Bravo-Cordero JJ, Miskolci V, Condeelis J, Hodgson L. A Trio-Rac1-Pak1 signalling axis drives invadopodia disassembly. Nat Cell Biol. 2015;17:350.
Neubrand VE, Thomas C, Schmidt S, Debant A, Schiavo G. Kidins220/ARMS regulates Rac1-dependent neurite outgrowth by direct interaction with the RhoGEF Trio. J Cell Sci. 2010;123:2111–23.
Pengelly RJ, Greville-Heygate S, Schmidt S, Seaby EG, Jabalameli MR, Mehta SG, Parker MJ, Goudie D, Fagotto-Kaufmann C, Mercer C, Study DDD, Debant A, Ennis S, Baralle D. Mutations specific to the Rac-GEF domain of TRIO cause intellectual disability and microcephaly. J Med Genet. 2016;53(11):735–742.
Peurois F, Veyron S, Ferrandez Y, Ladid I, Benabdi S, Zeghouf M, Peyroche G, Cherfils J. Characterization of the activation of small GTPases by their GEFs on membranes using artificial membrane tethering. Biochem J. 2017;474(7):1259–1272.
Rojas RJ, Yohe ME, Gershburg S, Kawano T, Kozasa T, Sondek J. G-alpha-q directly activates p63RhoGEF and Trio via a conserved extension of the DH-associated PH domain. J Biol Chem. 2007;282(40):29201–10.
Schmidt S, Debant A. Function and regulation of the Rho guanine nucleotide exchange factor Trio. Small GTPases. 2014;5:e29769.
Steven R, Kubiseski TJ, Zheng H, Kulkarni S, Mancillas J, Ruiz Morales A, Hogue CW, Pawson T, Culotti J. UNC-73 activates the Rac GTPase and is required for cell and growth cone migrations in C. elegans. Cell. 1998;92:785–95.
Van Haren J, Boudeau J, Schmidt S, Basu S, Liu Z, Lammers D, Demmers J, Benhari J, Grosveld F, Debant A, Galjart N. Dynamic microtubules catalyze formation of navigator-TRIO complexes to regulate neurite extension. Curr Biol. 2014;24:1778–85.
Van Rijssel J, Kroon J, Hoogenboezem M, Van Alphen FP, De Jong RJ, Kostadinova E, Geerts D, Hordijk PL, Van Buul JD. The Rho-guanine nucleotide exchange factor Trio controls leukocyte transendothelial migration by promoting docking structure formation. Mol Biol Cell. 2012;23:2831–44.
Van Rijssel J, Timmerman I, Van ALPHEN FP, Hoogenboezem M, Korchynskyi O, Geerts D, Geissler J, Reedquist KA, Niessen HW, Van Buul JD. The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2. Biol Open. 2013;2:569–79.
Vaque JP, Dorsam RT, Feng X, Iglesias-Bartolome R, Forsthoefel DJ, Chen Q, Debant A, Seeger MA, Ksander BR, Teramoto H, Gutkind JS. A genome-wide RNAi screen reveals a Trio-regulated Rho GTPase circuitry transducing mitogenic signals initiated by G protein-coupled receptors. Mol Cell. 2013;49:94–108.
Yano t, Yamazaki Y, Adachi M, Okawa K, Fort P, Uji M, Tsukita S, Tsukita S. Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling. J Cell Biol. 2011;193:319–32.
Zong W, Liu S, Wang X, Zhang J, Zhang T, Liu Z, Wang D, Zhang A, Zhu M, Gao J. Trio gene is required for mouse learning ability. Brain Res. 2015;1608:82–90.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Boudeau, J., Schmidt, S., Debant, A. (2018). Trio. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101658
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101658
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences