title: Connecting G protein signaling to chemoattractant-mediated cell polarity and cytoskeletal reorganization.
abstract: The 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.
authors.affiliation: a Department of Cell Biochemistry , University of Groningen , Groningen , The Netherlands.
authors.forename: Youtao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: b Section of Cell and Developmental Biology, Division of Biological Sciences, University of California , San Diego, La Jolla , CA , USA.
authors.forename: Jesus
authors.identifier: 0000-0002-2751-7291
authors.initials: J
authors.lastname: Lacal
authors.affiliation: b Section of Cell and Developmental Biology, Division of Biological Sciences, University of California , San Diego, La Jolla , CA , USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Firtel
authors.affiliation: a Department of Cell Biochemistry , University of Groningen , Groningen , The Netherlands.
authors.forename: Arjan
authors.identifier: 0000-0001-8174-6397
authors.initials: A
authors.lastname: Kortholt
mesh_terms: D000818:Animals; D016764:Cell Polarity; D002633:Chemotaxis; D003599:Cytoskeleton / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans
chemical_list: D019204:GTP-Binding Proteins
keywords: Dictyostelium; GPCRs; Rap; Ras; TORC2; chemotaxis; cytoskeleton rearrangements; heterotrimeric G proteins; proteomics; small G proteins