奥地利科学与技术研究所Carl-Philipp Heisenberg及其团队发现，紧密连接的机械感知依赖于ZO-1蛋白的相转换和流动。该研究成果于10月31日发表在国际学术期刊《细胞》。
 
研究人员表示，细胞间连接通过改变其组织和功能来响应机械力。
 
为了深入了解连接机械敏感性的机械化学基础，研究人员分析了斑马鱼胚胎中包膜细胞层（EVL）和卵黄合胞体层（YSL）之间的紧密结（TJ）形成。研究人员发现在TJ的Zonula Occludens-1（ZO-1）蛋白的积累与相邻肌动球蛋白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内的逆行性肌动球蛋白流动来触发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簇通过相分离形成，而ZO-1与肌动蛋白的直接结合则是将逆行流动的ZO-1簇稳定掺入TJ所必需的。如果ZO-1簇的形成和/或结合处受损，则TJ失去机械敏感性，从而EVL-YSL运动被延迟。因此，相分离和非连接ZO-1的流动赋予了TJ机械敏感性。

附：英文原文

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

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

Issue&Volume: 2019/10/31

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.

DOI: 10.1016/j.cell.2019.10.006

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31122-5