Connecting G protein signaling to chemoattractant-mediated cell polarity and cytoskeletal reorganization

Youtao Liu,Jesus Lacal,Richard A Firtel,Arjan Kortholt

doi:10.1080/21541248.2016.1235390

Youtao Liu, Jesus Lacal + Show 2 more

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https://doi.org/10.1080/21541248.2016.1235390

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Abstract

ABSTRACTThe directional movement toward extracellular chemical gradients, a process called chemotaxis, is an important property of cells. Central to eukaryotic chemotaxis is the molecular mechanism by which chemoattractant-mediated activation of G-protein coupled receptors (GPCRs) induces symmetry breaking in the activated downstream signaling pathways. Studies with mainly Dictyostelium and mammalian neutrophils as experimental systems have shown that chemotaxis is mediated by a complex network of signaling pathways. Recently, several labs have used extensive and efficient proteomic approaches to further unravel this dynamic signaling network. Together these studies showed the critical role of the interplay between heterotrimeric G-protein subunits and monomeric G proteins in regulating cytoskeletal rearrangements during chemotaxis. Here we highlight how these proteomic studies have provided greater insight into the mechanisms by which the heterotrimeric G protein cycle is regulated, how heterotrimeric G proteins-induced symmetry breaking is mediated through small G protein signaling, and how symmetry breaking in G protein signaling subsequently induces cytoskeleton rearrangements and cell migration.

Highlights

Chemotaxis, or directional movement toward extracellular gradient of chemicals, is fundamentally important for processes as diverse as innate immune responses to bacterial infections, finding nutrients, and organizing embryonic structures.[1]
It is clear that chemotaxis in amoeboid cells, such as neutrophils and Dictyostelium cells, starts with binding of the chemoattractant to cell-surface G-protein coupled receptors (GPCRs)
How is the heterotrimeric G protein cycle regulated to provide the spatial outputs of Ga and Gbg? What are the mechanisms by which heterotrimeric G proteins induce activation of monomeric G proteins? What are the connecting components of the core chemotaxis pathway? How is G protein signaling coupled to activation of cytoskeletal elements and subsequently cell movement? We, and others, have adopted comprehensive proteomic approaches to identify additional components of the chemotaxis pathways in order to answer the questions addressed above (Fig. 1).[20,21,22]

Summary

Introduction

Chemotaxis, or directional movement toward extracellular gradient of chemicals, is fundamentally important for processes as diverse as innate immune responses to bacterial infections, finding nutrients, and organizing embryonic structures.[1]. KEYWORDS chemotaxis; cytoskeleton rearrangements; Dictyostelium; GPCRs; heterotrimeric G proteins; proteomics; Ras; Rap; small G proteins; TORC2

Results

Conclusion