bims-fascar 2019-11-03 papers

on Phase separation and cellular architecture

Issue of 2019–11–03
two papers selected by
Victoria Tianjing Yan, Max Planck Institute of Molecular Cell Biology and Genetics

Phase Separation of Zonula Occludens Proteins Drives Formation of Tight Junctions.
Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.

Cell. 2019 Oct 31. pii: S0092-8674(19)31127-4. [Epub ahead of print]179(4): 923-936.e11

Phase Separation of Zonula Occludens Proteins Drives Formation of Tight Junctions.

Oliver Beutel, Riccardo Maraspini, Karina Pombo-García, Cécilie Martin-Lemaitre, Alf Honigmann.

  Tight junctions are cell-adhesion complexes that seal tissues and are involved in cell polarity and signaling. Supra-molecular assembly and positioning of tight junctions as continuous networks of adhesion strands are dependent on the membrane-associated scaffolding proteins ZO1 and ZO2. To understand how zona occludens (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.

Keywords:  cell adhesion; membrane scaffold; phase separation; self-organization; supra-molecular assembly; tight junction; zonula occludens

DOI:  https://doi.org/10.1016/j.cell.2019.10.011
Cell. 2019 Oct 31. pii: S0092-8674(19)31122-5. [Epub ahead of print]179(4): 937-952.e18

Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.

Cornelia Schwayer, Shayan Shamipour, Kornelija Pranjic-Ferscha, Alexandra Schauer, Maria Balda, Masazumi Tada, Karl Matter, Carl-Philipp Heisenberg.

  Cell-cell junctions respond to mechanical forces by changing their organization and function. To gain insight into the mechanochemical basis underlying junction mechanosensitivity, we analyzed tight junction (TJ) formation between the enveloping cell layer (EVL) and the yolk syncytial layer (YSL) in the gastrulating zebrafish embryo. We found that the accumulation of Zonula Occludens-1 (ZO-1) at TJs closely scales with tension of the adjacent actomyosin network, revealing that these junctions are mechanosensitive. Actomyosin tension triggers ZO-1 junctional accumulation by driving retrograde actomyosin flow within the YSL, which transports non-junctional ZO-1 clusters toward the TJ. Non-junctional ZO-1 clusters form by phase separation, and direct actin binding of ZO-1 is required for stable incorporation of retrogradely flowing ZO-1 clusters into TJs. If the formation and/or junctional incorporation of ZO-1 clusters is impaired, then TJs lose their mechanosensitivity, and consequently, EVL-YSL movement is delayed. Thus, phase separation and flow of non-junctional ZO-1 confer mechanosensitivity to TJs.

Keywords:  ZO-1; actomyosin flow; mechanosensation; phase separation; tight junction; zebrafish

DOI:  https://doi.org/10.1016/j.cell.2019.10.006