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

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.

journal_name

Cell

journal_title

Cell

authors

Schwayer C,Shamipour S,Pranjic-Ferscha K,Schauer A,Balda M,Tada M,Matter K,Heisenberg CP

doi

10.1016/j.cell.2019.10.006

subject

Has Abstract

pub_date

2019-10-31 00:00:00

pages

937-952.e18

issue

4

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(19)31122-5

journal_volume

179

pub_type

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