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Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.
Cell ( IF 45.5 ) Pub Date : 2019-10-31 , DOI: 10.1016/j.cell.2019.10.006 Cornelia Schwayer 1 , Shayan Shamipour 1 , Kornelija Pranjic-Ferscha 1 , Alexandra Schauer 1 , Maria Balda 2 , Masazumi Tada 3 , Karl Matter 2 , Carl-Philipp Heisenberg 1
Cell ( IF 45.5 ) Pub Date : 2019-10-31 , DOI: 10.1016/j.cell.2019.10.006 Cornelia Schwayer 1 , Shayan Shamipour 1 , Kornelija Pranjic-Ferscha 1 , Alexandra Schauer 1 , Maria Balda 2 , Masazumi Tada 3 , Karl Matter 2 , Carl-Philipp Heisenberg 1
Affiliation
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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.
中文翻译：
紧结的机械传感取决于ZO-1相分离和流动。
细胞间连接通过改变其组织和功能来响应机械力。为了深入了解结机械敏感性的机械化学基础，我们分析了斑马鱼胚胎中包膜细胞层（EVL）和卵黄合胞体层（YSL）之间紧密连接（TJ）的形成。我们发现Zonula Occludens-1（ZO-1）在TJs的积累与邻近的放线菌素网络的张力紧密相关，表明这些连接点是机械敏感的。肌动球蛋白的张力通过驱动YSL内逆行性肌动球蛋白的流动来触发ZO-1的连接积累，从而将非连接的ZO-1簇向TJ输送。非连接的ZO-1簇是通过相分离形成的，ZO-1的直接肌动蛋白结合是将逆行流动的ZO-1簇稳定掺入TJ中所必需的。如果ZO-1簇的形成和/或连接结合受损，则TJ失去机械敏感性，因此，EVL-YSL运动被延迟。因此，相交和非结ZO-1的流动赋予TJ机械敏感性。
更新日期：2019-11-09
中文翻译：
紧结的机械传感取决于ZO-1相分离和流动。
细胞间连接通过改变其组织和功能来响应机械力。为了深入了解结机械敏感性的机械化学基础，我们分析了斑马鱼胚胎中包膜细胞层（EVL）和卵黄合胞体层（YSL）之间紧密连接（TJ）的形成。我们发现Zonula Occludens-1（ZO-1）在TJs的积累与邻近的放线菌素网络的张力紧密相关，表明这些连接点是机械敏感的。肌动球蛋白的张力通过驱动YSL内逆行性肌动球蛋白的流动来触发ZO-1的连接积累，从而将非连接的ZO-1簇向TJ输送。非连接的ZO-1簇是通过相分离形成的，ZO-1的直接肌动蛋白结合是将逆行流动的ZO-1簇稳定掺入TJ中所必需的。如果ZO-1簇的形成和/或连接结合受损，则TJ失去机械敏感性，因此，EVL-YSL运动被延迟。因此，相交和非结ZO-1的流动赋予TJ机械敏感性。
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