High Throughput strategies Aimed at Closing the GAP in Our Knowledge of Rho GTPase Signaling

Manel Dahmene,Laura Quirion,Mélanie Laurin

doi:10.3390/cells9061430

Manel Dahmene, Laura Quirion + Show 1 more

Open Access

https://doi.org/10.3390/cells9061430

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Journal: Cells	Publication Date: Jun 9, 2020
Citations: 8	License type: CC BY 4.0

Affiliation: Université Laval, Montreal Clinical Research Institute

Abstract

Since their discovery, Rho GTPases have emerged as key regulators of cytoskeletal dynamics. In humans, there are 20 Rho GTPases and more than 150 regulators that belong to the RhoGEF, RhoGAP, and RhoGDI families. Throughout development, Rho GTPases choregraph a plethora of cellular processes essential for cellular migration, cell–cell junctions, and cell polarity assembly. Rho GTPases are also significant mediators of cancer cell invasion. Nevertheless, to date only a few molecules from these intricate signaling networks have been studied in depth, which has prevented appreciation for the full scope of Rho GTPases’ biological functions. Given the large complexity involved, system level studies are required to fully grasp the extent of their biological roles and regulation. Recently, several groups have tackled this challenge by using proteomic approaches to map the full repertoire of Rho GTPases and Rho regulators protein interactions. These studies have provided in-depth understanding of Rho regulators specificity and have contributed to expand Rho GTPases’ effector portfolio. Additionally, new roles for understudied family members were unraveled using high throughput screening strategies using cell culture models and mouse embryos. In this review, we highlight theses latest large-scale efforts, and we discuss the emerging opportunities that may lead to the next wave of discoveries.

Highlights

Rho GTPases, which are best known for their regulation of the actin cytoskeleton, play central roles in many physiological and pathological processes [1]
Due to their capacity to orchestrate the formation of tissue architecture, Rho GTPases have emerged as fundamental regulators of morphogenesis during embryonic development [2]
Several groups have relied on RNA interference (RNAi) screens to systematically test the requirement of Rho GTPases, RhoGEFs, RhoGAPs, and RhoGDIs in distinct biological processes

Summary

Introduction

Rho GTPases, which are best known for their regulation of the actin cytoskeleton, play central roles in many physiological and pathological processes [1] Due to their capacity to orchestrate the formation of tissue architecture, Rho GTPases have emerged as fundamental regulators of morphogenesis during embryonic development [2]. GTPases signaling networks, only large-scale global approaches are how likely to mitigate stimuli that gap converge on the sameRecently, Rho GTPase trigger proteomic different responses in cells and the contributed repertoire to for this current in knowledge. Several crosstalk between Rho GTPases signaling networks, only large-scale global approaches are likely to groups have exploited high throughput screening approaches to identify new functional roles for mitigate for this current gap in knowledge.

Rho GTPases Cycle and their Regulation

Discussion

Findings

Methods