Uechi, H., Sun, D., Saeki, Y., Hiraiwa, T., Honigmann, A., Hyman, A.A., Kuranaga, E. (2026). A conserved motif tunes Sidekick condensate dynamics to control tricellular junction recruitment during epithelial remodeling.  Cell Rep. 45(5): 117336.

FBrf0265463

Research paper

The tricellular junction, where three or more cells contact, comprises specific proteins regulating epithelial morphogenesis and homeostasis. It remains elusive how these proteins are confined to tricellular junctions to function. We reveal that the intracellular domain of the adhesive transmembrane protein Sidekick forms condensates and contributes to its accumulation at tricellular junctions. Fly genetics and in vitro reconstitution indicate that condensation alone is not sufficient for targeting but promotes stable accumulation of Sidekick at physiological concentrations. We identify a conserved motif whose deletion increases condensate dynamics and leads to mislocalization of Sidekick during epithelial junction remodeling. Mislocalization is accompanied by disturbed recruitment of Sidekick-associating proteins involved in junction dynamics to tricellular junctions and leads to delay in junction formation. These findings suggest that condensates with relatively low internal dynamics stabilize Sidekick localization under tissue dynamics, which assists recruitment of junction dynamics-regulating proteins and ensures epithelial remodeling.