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Membrane prewetting by condensates promotes tight-junction belt formation

Karina Pombo-García (), Omar Adame-Arana, Cecilie Martin-Lemaitre, Frank Jülicher and Alf Honigmann ()
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Karina Pombo-García: Max Planck Institute of Molecular Cell Biology and Genetics
Omar Adame-Arana: Max Planck Institute for the Physics of Complex Systems
Cecilie Martin-Lemaitre: Max Planck Institute of Molecular Cell Biology and Genetics
Frank Jülicher: Max Planck Institute for the Physics of Complex Systems
Alf Honigmann: Max Planck Institute of Molecular Cell Biology and Genetics

Nature, 2024, vol. 632, issue 8025, 647-655

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41586-024-07726-0

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