PUBLICATION
Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow
- Authors
- Schwayer, C., Shamipour, S., Pranjic-Ferscha, K., Schauer, A., Balda, M., Tada, M., Matter, K., Heisenberg, C.P.
- ID
- ZDB-PUB-191102-41
- Date
- 2019
- Source
- Cell 179: 937-952.e18 (Journal)
- Registered Authors
- Heisenberg, Carl-Philipp, Tada, Masazumi
- Keywords
- ZO-1, actomyosin flow, mechanosensation, phase separation, tight junction, zebrafish
- MeSH Terms
-
- Embryonic Development/genetics*
- Mechanotransduction, Cellular/genetics*
- Actin Cytoskeleton/genetics
- Yolk Sac/growth & development
- Yolk Sac/metabolism
- Gene Expression Regulation, Developmental/genetics
- Tight Junctions/genetics*
- Tight Junctions/physiology
- Animals, Genetically Modified/genetics
- Animals, Genetically Modified/growth & development
- Animals
- Zonula Occludens-1 Protein/genetics*
- Membrane Proteins/genetics
- Protein Binding
- Humans
- Actomyosin/genetics
- Embryo, Nonmammalian/physiology
- Phosphoproteins/genetics
- Zebrafish/genetics
- Zebrafish/growth & development
- Mice
- PubMed
- 31675500 Full text @ Cell
Citation
Schwayer, C., Shamipour, S., Pranjic-Ferscha, K., Schauer, A., Balda, M., Tada, M., Matter, K., Heisenberg, C.P. (2019) Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow. Cell. 179:937-952.e18.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping