title: RIC8 is a guanine-nucleotide exchange factor for Galpha subunits that regulates growth and development in Neurospora crassa.
abstract: Heterotrimeric (αβγ) G proteins are crucial components of eukaryotic signal transduction pathways. G-protein-coupled receptors (GPCRs) act as guanine nucleotide exchange factors (GEFs) for Gα subunits. Recently, facilitated GDP/GTP exchange by non-GPCR GEFs, such as RIC8, has emerged as an important mechanism for Gα regulation in animals. RIC8 is present in animals and filamentous fungi, such as the model eukaryote Neurospora crassa, but is absent from the genomes of baker's yeast and plants. In Neurospora, deletion of ric8 leads to profound defects in growth and asexual and sexual development, similar to those observed for a mutant lacking the Gα genes gna-1 and gna-3. In addition, constitutively activated alleles of gna-1 and gna-3 rescue many defects of Δric8 mutants. Similar to reports in Drosophila, Neurospora Δric8 strains have greatly reduced levels of G-protein subunits. Effects on cAMP signaling are suggested by low levels of adenylyl cyclase protein in Δric8 mutants and suppression of Δric8 by a mutation in the protein kinase A regulatory subunit. RIC8 acts as a GEF for GNA-1 and GNA-3 in vitro, with the strongest effect on GNA-3. Our results support a role for RIC8 in regulating GNA-1 and GNA-3 in Neurospora.
authors.affiliation: Program in Biochemistry and Molecular Biology, Department of Plant Pathology and Microbiology, University of California, Riverside, CA 92521, USA.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Wright
authors.forename: Regina
authors.initials: R
authors.lastname: Inchausti
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Eaton
authors.forename: Svetlana
authors.initials: S
authors.lastname: Krystofova
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Borkovich
mesh_terms: D000595:Amino Acid Sequence; D000242:Cyclic AMP / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006151:Guanosine / Q000378:metabolism; D025301:Hyphae / Q000378:metabolism; D008969:Molecular Sequence Data; D009492:Neurospora crassa / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D021381:Protein Transport; D016415:Sequence Alignment; D015398:Signal Transduction; D013172:Spores, Fungal / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D044385:GTP-Binding Protein alpha Subunits; D020662:Guanine Nucleotide Exchange Factors; D006151:Guanosine; D000242:Cyclic AMP