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Mechanosensation of tight junctions depends on ZO-1 phase separation and flow

Item Type:Article
Title:Mechanosensation of tight junctions depends on ZO-1 phase separation and flow
Creators: Schwayer, Cornelia ORCID logoORCID: https://orcid.org/0000-0001-5130-2226, Shamipour, Shayan, Pranjic-Ferscha, Kornelija, Schauer, Alexandra, Balda, Maria, Tada, Masazumi, Matter, Karl and Heisenberg, Carl-Philipp
Abstract: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:Actin Cytoskeleton, Actomyosin, Cellular Mechanotransduction, Developmental Gene Expression Regulation, Embryonic Development, Genetically Modified Animals, Membrane Proteins, Nonmammalian Embryo, Phosphoproteins, Protein Binding, Tight Junctions, Yolk Sac, Zonula Occludens-1 Protein, Animals, Mice, Zebrafish
Source:Cell
ISSN:0092-8674
Publisher:Cell Press
Volume:179
Number:4
Page Range:937-952.e18
Date:31 October 2019
Official Publication:https://doi.org/10.1016/j.cell.2019.10.006
PubMed:View item in PubMed

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