title: Neuroglian, Gliotactin, and the Na+/K+ ATPase are essential for septate junction function in Drosophila.
abstract: One essential function of epithelia is to form a barrier between the apical and basolateral surfaces of the epithelium. In vertebrate epithelia, the tight junction is the primary barrier to paracellular flow across epithelia, whereas in invertebrate epithelia, the septate junction (SJ) provides this function. In this study, we identify new proteins that are required for a functional paracellular barrier in Drosophila. In addition to the previously known components Coracle (COR) and Neurexin (NRX), we show that four other proteins, Gliotactin, Neuroglian (NRG), and both the alpha and beta subunits of the Na+/K+ ATPase, are required for formation of the paracellular barrier. In contrast to previous reports, we demonstrate that the Na pump is not localized basolaterally in epithelial cells, but instead is concentrated at the SJ. Data from immunoprecipitation and somatic mosaic studies suggest that COR, NRX, NRG, and the Na+/K+ ATPase form an interdependent complex. Furthermore, the observation that NRG, a Drosophila homologue of vertebrate neurofascin, is an SJ component is consistent with the notion that the invertebrate SJ is homologous to the vertebrate paranodal SJ. These findings have implications not only for invertebrate epithelia and barrier functions, but also for understanding of neuron-glial interactions in the mammalian nervous system.
authors.affiliation: Department of Biology, Developmental, Cell, and Molecular Biology Group, Duke University, Durham, NC 27708, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Genova
authors.forename: Richard G
authors.initials: RG
authors.lastname: Fehon
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002462:Cell Membrane / Q000201:enzymology; D002874:Chromosome Mapping; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000201:enzymology* / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000201:enzymology* / Q000648:ultrastructure; D004848:Epithelium / Q000196:embryology / Q000201:enzymology* / Q000648:ultrastructure; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D007365:Intercellular Junctions / Q000201:enzymology* / Q000648:ultrastructure; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D008854:Microscopy, Electron; D009030:Mosaicism / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D009479:Neuropeptides; D021122:Protein Subunits / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D006023:Glycoproteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C094061:Nrv2 protein, Drosophila; D021122:Protein Subunits; C442474:cora protein, Drosophila; C094064:gliotactin; C112162:neurexophilin; C061745:Nrg protein, Drosophila; D000254:Sodium-Potassium-Exchanging ATPase