title: Dictyostelium Ric8 is a nonreceptor guanine exchange factor for heterotrimeric G proteins and is important for development and chemotaxis.
abstract: Heterotrimeric G proteins couple external signals to the activation of intracellular signal transduction pathways. Agonist-stimulated guanine nucleotide exchange activity of G-protein-coupled receptors results in the exchange of G-protein-bound GDP to GTP and the dissociation and activation of the complex into Gα-GTP and a Gβγ dimer. In Dictyostelium, a basal chemotaxis pathway consisting of heterotrimeric and monomeric G proteins is sufficient for chemotaxis. Symmetry breaking and amplification of chemoattractant sensing occurs between heterotrimeric G protein signaling and Ras activation. In a pull-down screen coupled to mass spectrometry, with Gα proteins as bait, we have identified resistant to inhibitors of cholinesterase 8 (Ric8) as a nonreceptor guanine nucleotide exchange factor for Gα-protein. Ric8 is not essential for the initial activation of heterotrimeric G proteins or Ras by uniform chemoattractant; however, it amplifies Gα signaling, which is essential for Ras-mediated symmetry breaking during chemotaxis and development.
authors.affiliation: Department of Cell Biochemistry, University of Groningen, 9747 AG Groningen, The Netherlands.
authors.forename: Rama
authors.initials: R
authors.lastname: Kataria
authors.forename: Xuehua
authors.initials: X
authors.lastname: Xu
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Fusetti
authors.forename: Ineke
authors.initials: I
authors.lastname: Keizer-Gunnink
authors.forename: Tian
authors.initials: T
authors.lastname: Jin
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: van Haastert
authors.forename: Arjan
authors.initials: A
authors.lastname: Kortholt
mesh_terms: D002633:Chemotaxis / Q000235:genetics* / Q000502:physiology; D004023:Dictyostelium / Q000235:genetics* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D015800:Protozoan Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D014741:Video Recording
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D015800:Protozoan Proteins; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins