title: A Gβγ effector, ElmoE, transduces GPCR signaling to the actin network during chemotaxis.
abstract: Activation of G protein-coupled receptors (GPCRs) leads to the dissociation of heterotrimeric G-proteins into Gα and Gβγ subunits, which go on to regulate various effectors involved in a panoply of cellular responses. During chemotaxis, Gβγ subunits regulate actin assembly and migration, but the protein(s) linking Gβγ to the actin cytoskeleton remains unknown. Here, we identified a Gβγ effector, ElmoE in Dictyostelium, and demonstrated that it is required for GPCR-mediated chemotaxis. Remarkably, ElmoE associates with Gβγ and Dock-like proteins to activate the small GTPase Rac, in a GPCR-dependent manner, and also associates with Arp2/3 complex and F-actin. Thus, ElmoE serves as a link between chemoattractant GPCRs, G-proteins and the actin cytoskeleton. The pathway, consisting of GPCR, Gβγ, Elmo/Dock, Rac, and Arp2/3, spatially guides the growth of dendritic actin networks in pseudopods of eukaryotic cells during chemotaxis.
authors.affiliation: Chemotaxis Signal Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Jianshe
authors.initials: J
authors.lastname: Yan
authors.forename: Vassil
authors.initials: V
authors.lastname: Mihaylov
authors.forename: Xuehua
authors.initials: X
authors.lastname: Xu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Brzostowski
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Lunhua
authors.initials: L
authors.lastname: Liu
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Carole A
authors.initials: CA
authors.lastname: Parent
authors.forename: Tian
authors.initials: T
authors.lastname: Jin
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002630:Chemotactic Factors; D002633:Chemotaxis / Q000502:physiology*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D004023:Dictyostelium / Q000502:physiology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D047468:Immunoprecipitation; D011485:Protein Binding; D021381:Protein Transport; D040901:Proteomics; D011953:Receptors, Cyclic AMP / Q000378:metabolism*; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D002630:Chemotactic Factors; D003432:Cross-Linking Reagents; D011953:Receptors, Cyclic AMP; C068125:cyclic AMP receptor cAR1; D000242:Cyclic AMP; D020962:Heterotrimeric GTP-Binding Proteins; D020744:rac GTP-Binding Proteins