Syntaxin 16 Regulates Lumen Formation during Epithelial Morphogenesis

Jung, J.J., Inamdar, S.M., Tiwari, A., Ye, D., Lin, F., and Choudhury, A.
PLoS One   8(4): e61857 (Journal)
Registered Authors
Lin, Fang, Ye, Ding
MeSH Terms
  • Animals
  • Cadherins/genetics
  • Cadherins/metabolism
  • Cell Count
  • Cell Membrane/metabolism
  • Cell Membrane/ultrastructure
  • Collagen
  • Dogs
  • Drug Combinations
  • Embryo, Nonmammalian
  • Endosomes/metabolism
  • Endosomes/ultrastructure
  • Gene Expression Regulation, Developmental*
  • Golgi Apparatus/metabolism
  • Golgi Apparatus/ultrastructure
  • Intercellular Junctions/genetics
  • Intercellular Junctions/metabolism*
  • Intercellular Junctions/ultrastructure
  • Kidney/growth & development
  • Kidney/metabolism*
  • Kidney/ultrastructure
  • Laminin
  • Madin Darby Canine Kidney Cells
  • Protein Transport
  • Proteoglycans
  • SNARE Proteins/genetics
  • SNARE Proteins/metabolism
  • Signal Transduction
  • Spindle Apparatus/metabolism
  • Spindle Apparatus/ultrastructure
  • Syntaxin 16/genetics
  • Syntaxin 16/metabolism*
  • Transgenes
  • Zebrafish
23626741 Full text @ PLoS One

The formation and maintenance of cell-cell junctions, both under physiological and pathological conditions, requires the targeting and trafficking of junctional proteins. Proteins of the syntaxin (Stx)-family localize to a variety of subcellular membranes and contribute to intracellular transport of cargo by regulating vesicle fusion events at these sites. Unlike plasma membrane localized Stxs, the roles of endosome- and Golgi-localized stx proteins in epithelial morphogenesis are less understood. Here we show that Stx16– an endosome- and Golgi-localized target-membrane soluble N-ethylmaleimide attachment protein receptor (t-SNARE) that plays a role in membrane trafficking between these compartments – is essential for lumen development. In cultured Madin Darby Canine Kidney (MDCK) cells, Stx16 was selectively upregulated as sparsely plated cells attained confluency. Stx16-depleted confluent monolayers consistently showed lower transepithelial resistance than control monolayers, and failed to maintain endogenous and ectopically expressed E-cadherin at the adherens junctions due to decreased recycling. We further found that whereas cysts formed by MDCK cells cultured in Matrigel have a single hollow lumen, those formed by stx16-depleted counterparts had multiple lumens, due to abnormal orientiation of the mitotic spindle. Finally, a similar role for stx16 function in vivo is indicated by our analysis of pronephric-duct development in zebrafish expressing the claudinB:lynGFP transgene; lack of stx16 function in this structure (in stx16-morphant embryos) led to the development of enlarged, torturous pronephric ducts with more than one lumen. Taken together, our in vitro and in vivo studies establish a role for Stx16 in maintaining the integrity of cell-cell junctions, and thereby in morphogenesis of the kidney epithelial lumen.

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