title: Assembly of C. elegans apical junctions involves positioning and compaction by LET-413 and protein aggregation by the MAGUK protein DLG-1.
abstract: Specialised subapical junctions play a critical role in maintaining epithelial cell polarity and tissue integrity, and provide a platform for intracellular signalling. Here we analyse the roles of C. elegans genes let-413 and dlg-1, a homologue of Drosophila lethal discs large, in the assembly of the C. elegans apical junction (CeAJ), and provide the first characterisation of this structure. We have identified dlg-1 as an essential gene in an RNA interference screen against C. elegans homologues of genes encoding proteins involved in tight or septate junction formation. We show that DLG-1 colocalises with the junctional protein JAM-1 at CeAJs in a unit distinct from HMP-1/alpha-catenin, and apical to the laterally localised LET-413. Loss of dlg-1 activity leads to JAM-1 mislocalisation and the disappearance of the electron-dense component of the CeAJs, but only mild adhesion and polarity defects. In contrast, loss of let-413 activity leads to the formation of basally extended discontinuous CeAJs and strong adhesion and polarity defects. Interestingly, in LET-413-deficient embryos, CeAJ markers are localised along the lateral membrane in a manner resembling that observed in wild-type embryos at the onset of epithelial differentiation. We conclude that the primary function of LET-413 is to correctly position CeAJ components at a discrete subapical position. Furthermore, we propose that DLG-1 is required to aggregate JAM-1 and other proteins forming the electron-dense CeAJ structure. Our data suggest that epithelial adhesion is maintained by several redundant systems in C. elegans.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP163, 1, rue Laurent Fries, 67404 Illkirch, France.
authors.forename: L
authors.initials: L
authors.lastname: McMahon
authors.forename: R
authors.initials: R
authors.lastname: Legouis
authors.forename: J L
authors.initials: JL
authors.lastname: Vonesch
authors.forename: M
authors.initials: M
authors.lastname: Labouesse
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D002454:Cell Differentiation; D016764:Cell Polarity; D004847:Epithelial Cells / Q000166:cytology* / Q000648:ultrastructure; D051528:Guanylate Kinases; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure; D051178:alpha Catenin
chemical_list: D029742:Caenorhabditis elegans Proteins; C000600734:HMP-1 protein, C elegans; D015801:Helminth Proteins; C413362:LET-413 protein, C elegans; D051178:alpha Catenin; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases