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Sidekick Is a Key Component of Tricellular Adherens Junctions that Acts to Resolve Cell Rearrangements

Letizia et al. characterize the nature and function of tricellular adherens junctions. The transmembrane protein Sidekick is highly enriched at these junctions and connects to the actin cytoskeleton through Canoe and Polychaetoid. This complex can sense and modulate tension to promote normal cell rearrangements during developmental remodeling.

Tricellular adherens junctions are points of high tension that are central to the rearrangement of epithelial cells. However, the molecular composition of these junctions is unknown, making it difficult to assess their role in morphogenesis. Here we show that Sidekick, an immunoglobulin family cell adhesion protein, is highly enriched at tricellular adherens junctions in Drosophila. This localization is modulated by tension, and Sidekick is itself necessary to maintain normal levels of cell bond tension. Loss of Sidekick causes defects in cell and junctional rearrangements in actively remodeling epithelial tissues like the retina and tracheal system. The adaptor proteins Polychaetoid and Canoe are enriched at tricellular adherens junctions in a Sidekick-dependent manner; Sidekick functionally interacts with both proteins and directly binds to Polychaetoid. We suggest that Polychaetoid and Canoe link Sidekick to the actin cytoskeleton to enable tricellular adherens junctions to maintain or transmit cell bond tension during epithelial cell

Letizia A, He D, Astigarraga S, Colombelli J, Hatini V, Llimargas M, Treisman JE. Dev Cell. 2019 Jul 25. pii: S1534-5807(19)30579-9. doi: 10.1016/j.devcel.2019.07.007.

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