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Phase Separation of Zonula Occludens Proteins Drives Formation of Tight Junctions

35 Pages Posted: 29 Mar 2019 Last revised: 8 Nov 2019 Sneak Peek Status: Published

See all articles by Oliver Beutel

Oliver Beutel

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)

Riccardo Maraspini

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)

Karina Pombo-Garcia

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)

Cecilie Martin-Lemaitre

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)

Alf Honigmann

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)

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Abstract

Tight junctions are cell adhesion complexes that seal tissues and are involved in cell polarity and signalling. Supra-molecular assembly and positioning of tight junctions as continuous networks of adhesion strands is dependent on the two membrane associated scaffolding proteins ZO1 and ZO2. To understand how ZO proteins organize junction assembly, we performed quantitative cell biology and in vitro reconstitution experiments. We discovered that ZO proteins self-organize membrane attached compartments via phase separation. We identified the multivalent interactions of the conserved PDZ-SH3-GuK supra-domain as the driver of phase separation. These interactions are regulated by phosphorylation and intra-molecular binding. Formation of condensed ZO protein compartments is sufficient to specifically enrich and localize tight junction proteins including adhesion receptors, cytoskeletal adapters and transcription factors. Our results suggest that an active phase transition of ZO proteins into a condensed membrane bound compartment drives claudin polymerization and coalescence of a continuous tight junction belt.

Suggested Citation

Beutel, Oliver and Maraspini, Riccardo and Pombo-Garcia, Karina and Martin-Lemaitre, Cecilie and Honigmann, Alf, Phase Separation of Zonula Occludens Proteins Drives Formation of Tight Junctions. Available at SSRN: https://ssrn.com/abstract=3362257 or http://dx.doi.org/10.2139/ssrn.3362257
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Oliver Beutel

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)

Pfotenhauerstr. 108
Dresden, 01307
Germany

Riccardo Maraspini

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)

Pfotenhauerstr. 108
Dresden, 01307
Germany

Karina Pombo-Garcia

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)

Pfotenhauerstr. 108
Dresden, 01307
Germany

Cecilie Martin-Lemaitre

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)

Pfotenhauerstr. 108
Dresden, 01307
Germany

Alf Honigmann (Contact Author)

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) ( email )

Pfotenhauerstr. 108
Dresden, 01307
Germany

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