The Triple-Repeat Protein Anakonda Controls Epithelial Tricellular Junction Formation in Drosophila

Dev Cell. 2015 Jun 8;33(5):535-48. doi: 10.1016/j.devcel.2015.03.023. Epub 2015 May 14.


In epithelia, specialized tricellular junctions (TCJs) mediate cell contacts at three-cell vertices. TCJs are fundamental to epithelial biology and disease, but only a few TCJ components are known, and how they assemble at tricellular vertices is not understood. Here we describe a transmembrane protein, Anakonda (Aka), which localizes to TCJs and is essential for the formation of tricellular, but not bicellular, junctions in Drosophila. Loss of Aka causes epithelial barrier defects associated with irregular TCJ structure and geometry, suggesting that Aka organizes cell corners. Aka is necessary and sufficient for accumulation of Gliotactin at TCJs, suggesting that Aka initiates TCJ assembly by recruiting other proteins to tricellular vertices. Aka's extracellular domain has an unusual tripartite repeat structure that may mediate self-assembly, directed by the geometry of tricellular vertices. Conversely, Aka's cytoplasmic tail is dispensable for TCJ localization. Thus, extracellular interactions, rather than TCJ-directed intracellular transport, appear to mediate TCJ assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics
  • Animals, Genetically Modified / growth & development
  • Animals, Genetically Modified / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism*
  • Embryo, Nonmammalian / cytology*
  • Embryo, Nonmammalian / metabolism
  • Epithelium / growth & development*
  • Epithelium / metabolism
  • Immunoblotting
  • Intercellular Junctions / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Protein Transport
  • Repetitive Sequences, Amino Acid
  • Tight Junctions / physiology*


  • Drosophila Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • gliotactin