Scribble and Discs-large mediate tricellular junction formation

Abstract

Junctional complexes that mediate cell adhesion are key to epithelial integrity, cell division and permeability barriers formation. In Drosophila the scaffolding proteins Scribble (Scrib) and Discs-large (Dlg) are key regulators of epithelial polarity, proliferation, assembly of junctions, and protein trafficking. We found that Scrib and Dlg are necessary for the formation of the tricellular junction (TCJ), a unique junction that forms in epithelia at the convergence of three neighbouring cells. Scrib and Dlg are in close proximity with the TCJ proteins Gliotactin (Gli) and Bark-beetle (Bark) and both are required for TCJ protein recruitment. Loss of Bark or Gli lead to the basolateral spread of the TCJ complex at the cell corners. Loss of the septate junction proteins NrxIV and the Na+/K+ ATPase also resulted in the basolateral spread of the entire TCJ complex at the cell corners. The Scrib PDZ1-2 domains and the Dlg GUK domain are necessary for Bark and Gli localization to the TCJ. Overall, we propose a model where Scrib and Dlg are key components of the TCJ, and form a complex with Bark and Gli.