title: IRI-1, a LIN-15B homologue, interacts with inositol-1,4,5-triphosphate receptors and regulates gonadogenesis, defecation, and pharyngeal pumping in Caenorhabditis elegans.
abstract: Inositol-1,4,5-triphosphate receptors (IP(3)Rs) are ligand-gated Ca(2+) channels that control Ca(2+) release from intracellular stores. They are central to a wide range of cellular responses. IP(3)Rs in Caenorhabditis elegans are encoded by a single gene, itr-1, and are widely expressed. Signaling through IP(3) and IP(3)Rs is important in ovulation, control of the defecation cycle, modulation of pharyngeal pumping rate, and embryogenesis. To further elucidate the molecular basis of the diversity of IP(3)R function, we used a yeast two-hybrid screen to search for proteins that interact with ITR-1. We identified an interaction between ITR-1 and IRI-1, a previously uncharacterized protein with homology to LIN-15B. Iri-1 is widely expressed, and its expression overlaps significantly with that of itr-1. In agreement with this observation, iri-1 functions in known itr-1-mediated processes, namely, upregulation of pharyngeal pumping in response to food and control of the defecation cycle. Knockdown of iri-1 in an itr-1 loss-of-function mutant potentiates some of these effects and sheds light on the signaling pathways that control pharyngeal pumping rate. Knockdown of iri-1 expression also results in a sterile, evl phenotype, as a consequence of failures in early Z1/Z4 lineage divisions, such that gonadogenesis is severely disrupted.
authors.affiliation: Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, United Kingdom.
authors.forename: Denise S
authors.initials: DS
authors.lastname: Walker
authors.forename: Sung
authors.initials: S
authors.lastname: Ly
authors.forename: Nicholas J D
authors.initials: NJ
authors.lastname: Gower
authors.forename: Howard A
authors.initials: HA
authors.lastname: Baylis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D003672:Defecation / Q000235:genetics / Q000502:physiology; D006066:Gonads / Q000737:chemistry / Q000254:growth & development; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008969:Molecular Sequence Data; D010614:Pharynx / Q000737:chemistry / Q000502:physiology; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics; D020798:Two-Hybrid System Techniques
chemical_list: D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; D002352:Carrier Proteins; C495589:GON-14 protein, C elegans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C088819:lin-15B protein, C elegans