RRC ID 57331
Author Sharifkhodaei Z, Padash-Barmchi M, Gilbert MM, Samarasekera G, Fulga TA, Van Vactor D, Auld VJ.
Title The Drosophila tricellular junction protein Gliotactin regulates its own mRNA levels through BMP-mediated induction of miR-184.
Journal J Cell Sci
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.
Volume 129(7)
Pages 1477-89
Published 2016-4-1
DOI 10.1242/jcs.178608
PII jcs.178608
PMID 26906422
PMC PMC4852718
MeSH Animals Apoptosis / physiology Bone Morphogenetic Proteins / metabolism* Cell Movement / physiology Cytokines / metabolism Drosophila Proteins / antagonists & inhibitors Drosophila Proteins / metabolism* Drosophila melanogaster / genetics* Endocytosis / physiology Enzyme Activation Membrane Proteins / genetics Membrane Proteins / metabolism* MicroRNAs / biosynthesis* MicroRNAs / genetics Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Protein Serine-Threonine Kinases / metabolism* RNA, Messenger / metabolism* Receptors, Cell Surface / metabolism* Serpins / metabolism Signal Transduction / genetics Tight Junctions / physiology
IF 4.517
Times Cited 4