title: Increased IP3/Ca2+ signaling compensates depletion of LET-413/DLG-1 in C. elegans epithelial junction assembly.
abstract: The let-413/scribble and dlg-1/discs large genes are key regulators of epithelial cell polarity in C. elegans and other systems but the mechanism how they organize a circumferential junctional belt around the apex of epithelial cells is not well understood. We report here that IP(3)/Ca(2+) signaling is involved in the let-413/dlg-1 pathway for the establishment of epithelial cell polarity during the development in C. elegans. Using RNAi to interfere with let-413 and dlg-1 gene functions during post-embryogenesis, we discovered a requirement for LET-413 and DLG-1 in the polarization of the spermathecal cells. The spermatheca forms an accordion-like organ through which eggs must enter to complete the ovulation process. LET-413- and DLG-1-depleted animals exhibit failure of ovulation. Consistent with this phenotype, the assembly of the apical junction into a continuous belt fails and the PAR-3 protein and microfilaments are no longer localized asymmetrically. All these defects can be suppressed by mutations in IPP-5, an inositol polyphosphate 5-phosphatase and in ITR-1, an inositol triphosphate receptor, which both are supposed to increase the intracellular Ca(2+) level. Analysis of embryogenesis revealed that IP(3)/Ca(2+) signaling is also required during junction assembly in embryonic epithelia.
authors.affiliation: Institute for Genetics, Heinrich-Heine-University Duesseldorf, D-40225 Duesseldorf, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pilipiuk
authors.forename: Christophe
authors.initials: C
authors.lastname: Lefebvre
authors.forename: Tobias
authors.initials: T
authors.lastname: Wiesenfahrt
authors.forename: Renaud
authors.initials: R
authors.lastname: Legouis
authors.forename: Olaf
authors.initials: O
authors.lastname: Bossinger
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D020013:Calcium Signaling; D016764:Cell Polarity; D047108:Embryonic Development; D004847:Epithelial Cells; D004848:Epithelium; D005260:Female; D051528:Guanylate Kinases / Q000502:physiology*; D007295:Inositol Phosphates / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism*; D008297:Male; D010060:Ovulation
chemical_list: D029742:Caenorhabditis elegans Proteins; D007295:Inositol Phosphates; C413362:LET-413 protein, C elegans; C530790:DLG-1 protein, C elegans; D051528:Guanylate Kinases