期刊
GENES & DEVELOPMENT
卷 21, 期 21, 页码 2731-2746出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1592007
关键词
G alpha(q); trio; rho; phospholipase c beta; C. elegans
The G alpha(q) 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 beta [PLC beta]) 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 G alpha(q) 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 beta). Strains containing null mutations in both EGL-8 (PLC beta) and UNC-73 ( Trio RhoGEF) have strong synthetic phenotypes that phenocopy the arrested growth and near-complete paralysis of G alpha(q)-null mutants. Using cell-based and biochemical assays, we show that activated C. elegans G alpha(q) synergizes with Trio RhoGEF to activate RhoA. Activated G alpha(q) 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 G alpha(q) effector that, together with PLC beta, mediates the G alpha(q) signaling that drives the locomotion, egg laying, and growth of the animal.
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