title: The Drosophila tricellular junction protein Gliotactin regulates its own mRNA levels through BMP-mediated induction of miR-184.
abstract: Epithelial bicellular and tricellular junctions are essential for establishing and maintaining permeability barriers. Tricellular junctions are formed by the convergence of three bicellular junctions at the corners of neighbouring epithelia. Gliotactin, a member of the Neuroligin family, is located at theDrosophilatricellular junction, and is crucial for the formation of tricellular and septate junctions, as well as permeability barrier function. Gliotactin protein levels are tightly controlled by phosphorylation at tyrosine residues and endocytosis. Blocking endocytosis or overexpressing Gliotactin results in the spread of Gliotactin from the tricellular junction, resulting in apoptosis, delamination and migration of epithelial cells. We show that Gliotactin levels are also regulated at the mRNA level by micro (mi)RNA-mediated degradation and that miRNAs are targeted to a short region in the 3'UTR that includes a conserved miR-184 target site. miR-184 also targets a suite of septate junction proteins, including NrxIV, coracle and Mcr. miR-184 expression is triggered when Gliotactin is overexpressed, leading to activation of the BMP signalling pathway. Gliotactin specifically interferes with Dad, an inhibitory SMAD, leading to activation of the Tkv type-I receptor and activation of Mad to elevate the biogenesis and expression of miR-184.
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver BC V6T 1Z3, Canada.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Sharifkhodaei
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver BC V6T 1Z3, Canada.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Padash-Barmchi
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver BC V6T 1Z3, Canada.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Gilbert
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver BC V6T 1Z3, Canada.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Samarasekera
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Tudor A
authors.initials: TA
authors.lastname: Fulga
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Van Vactor
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver BC V6T 1Z3, Canada auld@zoology.ubc.ca.
authors.forename: Vanessa J
authors.initials: VJ
authors.lastname: Auld
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D004705:Endocytosis / Q000502:physiology; D004789:Enzyme Activation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D019108:Tight Junctions / Q000502:physiology
chemical_list: D019485:Bone Morphogenetic Proteins; D016207:Cytokines; C108633:Dad protein, Drosophila; D029721:Drosophila Proteins; C509407:Mcr protein, Drosophila; D008565:Membrane Proteins; D035683:MicroRNAs; C543184:Mirn184 microRNA, Drosophila; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D015843:Serpins; C442474:cora protein, Drosophila; C094064:gliotactin; C090169:tkv protein, Drosophila; D017346:Protein Serine-Threonine Kinases
keywords: BMP; Tricellular junction; miRNA