Trio’s Rho-specific GEF domain is the missing Gαq effector in C. elegans

By Stacey L. Williams, Susanne Lutz, Nicole K. Charlie, C. Vettel, M. Ailion, C. Coco, John J. G. Tesmer, E. Jorgensen, T. Wieland, K. Miller. 2007

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The Gq pathway is essential for animal life and is a central pathway for driving locomotion, egg laying, and growth in Caenorhabditis elegans, where it exerts its effects through EGL-8 (phospholipase C [PLC]) and at least one other effector. To find the missing effector, we performed forward genetic screens to suppress the slow growth and hyperactive behaviors of mutants with an overactive Gq pathway. Four suppressor mutations disrupted the Rho-specific guanine-nucleotide exchange factor (GEF) domain of UNC-73 (Trio). The mutations produce defects in neuronal function, but not neuronal development, that cause sluggish locomotion similar to animals lacking EGL-8 (PLC). Strains containing null mutations in both EGL-8 (PLC) and UNC-73 (Trio RhoGEF) have strong synthetic phenotypes that phenocopy the arrested growth and near-complete paralysis of Gq-null mutants. Using cell-based and biochemical assays, we show that activated C. elegans Gq synergizes with Trio RhoGEF to activate RhoA. Activated Gq and Trio RhoGEF appear to be part of a signaling complex, because they coimmunoprecipitate when expressed together in cells. Our results show that Trio’s Rho-specific GEF domain is a major Gq effector that, together with PLC, mediates the Gq signaling that drives the locomotion, egg laying, and growth of the animal.

Subfields: Aging, Endocrine and Autonomic Systems, Social Psychology

View Paper: https://www.semanticscholar.org/paper/837dc60e5d1eaab5577bd4eb20a75caa61f7c8d0