Epithelial cells are polarized, with apical and basal compartments. demarcated by tight and adherens junctions. Specialized subapical junctions. play a critical role in maintaining epithelial cell polarity and tissue. integrity and provide a platform for intracellular signaling.. 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 molecular. mechanism by which they organize a circumferential junctional belt is not. known.. C. elegans LET-413, DLG-1, and AJM-1 play a fundamental role in. establishing the CeAJ in the C. elegans embryo, but to date the mechanisms. how the LET-413 protein correctly localizes the DLG-1-AJM-1 complex (DAC). and how the DAC then organizes a continuous junctional belt around the apex. of epithelial cells are still elusive. Moreover, during morphogenesis and. elongation process, the cadherin-catenin complex (CCC) is required and. regulates epithelial cell adhesion. As ventral enclosure completes,. circumferentially oriented actin bundles in the epidermis become anchored. into the CCC, and are thought to help to distribute the forces that. elongate the embryo.. After elimination of
let-413 function, the localization of the DAC is. retarded, finally causing an embryonic lethal phenotype.. Analysis of the role of
let-413/dlg-1 pathway during larval development. revealed a novel function of IP3/Ca2+ signaling in epithelial development. (see abstract by Pilipiuk et al.).. We report here the interactions between
let-413/dlg-1 pathway and IP3/Ca2+. signaling during the establishment of epithelial junctions in C. elegans. embryo.. We discovered that mutations in IPP-5, an inositol polyphosphate 5-. phosphatase and in ITR-1, an inositol triphosphate receptor can suppress. the cellular and the developmental defects of
let-413(RNAi) and dlg-. 1(RNAi). Both
ipp-5(gof) and
itr-1(lof) are supposed to increase the. intracellular Ca2+ level. The role of Ca2+ in
let-413/dlg-1 pathway was. also confirmed using the Ca2+ chelator EGTA. Surprisingly,
let-413(null). mutations are not suppressed by
ipp-5 and
itr-1, suggesting that a minimal. amount of LET-413 is necessary for rescue.. Our data suggest that
let-413/dlg-1 and Ca2+ signaling are involved in the. establishment of the cadherin-catenin complex during epithelial. polarization.