title: The CRAL/TRIO and GOLD domain protein CGR-1 promotes induction of vulval cell fates in Caenorhabditis elegans and interacts genetically with the Ras signaling pathway.
abstract: Ras-mediated signaling is necessary for the induction of vulval cell fates during Caenorhabditis elegans development. We identified cgr-1 by screening for suppressors of the ectopic vulval cell fates caused by a gain-of-function mutation of the let-60 ras gene. Analysis of two cgr-1 loss-of-function mutations indicates that cgr-1 positively regulates induction of vulval cell fates. cgr-1 is likely to function at a step in the Ras signaling pathway that is downstream of let-60, which encodes Ras, and upstream of lin-1, which encodes a transcription factor, if these genes function in a linear signaling pathway. These genetic studies are also consistent with the model that cgr-1 functions in a parallel pathway that promotes vulval cell fates. Localized expression studies suggest that cgr-1 functions cell autonomously to affect vulval cell fates. cgr-1 also functions early in development, since cgr-1 is necessary for larval viability. CGR-1 contains a CRAL/TRIO domain likely to bind a small hydrophobic ligand and a GOLD domain that may mediate interactions with proteins. A bioinformatic analysis revealed that there is a conserved family of CRAL/TRIO and GOLD domain-containing proteins that includes members from vertebrates and Drosophila. The analysis of cgr-1 identifies a novel in vivo function for a member of this family and a potential new regulator of Ras-mediated signaling.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Goldstein
authors.forename: Danielle
authors.initials: D
authors.lastname: Glossip
authors.forename: Sudhir
authors.initials: S
authors.lastname: Nayak
authors.forename: Kerry
authors.initials: K
authors.lastname: Kornfeld
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017124:Conserved Sequence; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007814:Larva / Q000166:cytology / Q000254:growth & development; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D017384:Sequence Deletion; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014844:Vulva / Q000166:cytology* / Q000196:embryology* / Q000254:growth & development; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C511072:CGR-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; C099628:TRIO protein, human; D018631:ras Proteins