Membrane prewetting by condensates promotes tight-junction belt formation

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Karina Pombo-García - , Max Planck Institute of Molecular Cell Biology and Genetics, Rosalind Franklin Institute (Author)
  • Omar Adame-Arana - , Max-Planck-Institute for the Physics of Complex Systems (Author)
  • Cecilie Martin-Lemaitre - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Frank Jülicher - , Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD), TUD Dresden University of Technology (Author)
  • Alf Honigmann - , Biotechnology Center, Clusters of Excellence PoL: Physics of Life, Chair of Biophysics, Max Planck Institute of Molecular Cell Biology and Genetics (Author)

Abstract

Biomolecular condensates enable cell compartmentalization by acting as membraneless organelles1. How cells control the interactions of condensates with other cellular structures such as membranes to drive morphological transitions remains poorly understood. We discovered that formation of a tight-junction belt, which is essential for sealing epithelial tissues, is driven by a wetting phenomenon that promotes the growth of a condensed ZO-1 layer2 around the apical membrane interface. Using temporal proximity proteomics in combination with imaging and thermodynamic theory, we found that the polarity protein PATJ mediates a transition of ZO-1 into a condensed surface layer that elongates around the apical interface. In line with the experimental observations, our theory of condensate growth shows that the speed of elongation depends on the binding affinity of ZO-1 to the apical interface and is constant. Here, using PATJ mutations, we show that ZO-1 interface binding is necessary and sufficient for tight-junction belt formation. Our results demonstrate how cells exploit the collective biophysical properties of protein condensates at membrane interfaces to shape mesoscale structures.

Details

Original languageEnglish
Pages (from-to)647-655
Number of pages9
JournalNature
Volume632
Issue number8025
Publication statusPublished - 15 Aug 2024
Peer-reviewedYes

External IDs

PubMed 39112699
ORCID /0000-0003-0475-3790/work/166324049

Keywords

ASJC Scopus subject areas