A conserved motif tunes Sidekick condensate dynamics to control tricellular junction recruitment during epithelial remodeling

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Hiroyuki Uechi - , Max Planck Institute of Molecular Cell Biology and Genetics, Tohoku University, Kyoto University (Author)
  • Daxiao Sun - , Chair of Biophysics, Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Yuki Saeki - , Tohoku University (Author)
  • Tetsuya Hiraiwa - , Academia Sinica - Institute of Physics (Author)
  • Alf Honigmann - , Chair of Biophysics, Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Anthony A. Hyman - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Erina Kuranaga - , Tohoku University, Kyoto University (Author)

Abstract

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.

Details

Original languageEnglish
Article number117336
JournalCell reports
Volume45
Issue number5
Publication statusPublished - 26 May 2026
Peer-reviewedYes

External IDs

ORCID /0000-0003-0475-3790/work/216557643

Keywords

Keywords

  • biomolecular condensation, epithelial morphogenesis, tricellular junctions