德国马普分子细胞生物学与遗传学研究所Alf Honigmann及其研究组发现，Zonula Occludens蛋白的相转换促使紧密连接的形成。10月31日，国际学术期刊《细胞》发表了这项研究成果。
 
为了了解ZO（zona occludens）蛋白如何组织连接组装，研究人员进行了定量细胞生物学和体外重构实验。研究人员发现，ZO蛋白通过相分离自组织膜附着区室。研究人员确定了保守的PDZ-SH3-GuK超结构域的多价相互作用是相分离的驱动因素。这些相互作用通过磷酸化和分子内结合来调节。浓缩ZO蛋白区室的形成足以特异性富集和定位紧密连接的蛋白质，包括粘附受体、细胞骨架衔接蛋白和转录因子。这些结果表明，ZO蛋白主动相转换为浓缩的膜结合区室，从而驱动了claudin聚合以及连续紧密连接带的聚结。
 
据介绍，紧密连接是密封组织的细胞粘附复合物，并参与细胞极性和信号传导。作为粘附链的连续网络的超分子组装和紧密连接的定位取决于膜相关的支架蛋白ZO1和ZO2。

附：英文原文

Title: Phase Separation of Zonula Occludens Proteins Drives Formation of Tight Junctions

Author: Oliver Beutel, Riccardo Maraspini, Karina Pombo-García, Cécilie Martin-Lemaitre, Alf Honigmann

Issue&Volume: 2019/10/31

Abstract: Tight junctions are cell-adhesion complexes that seal tissues and are involved in cell polarity and signaling. Supra-molecular assembly and positioning of tight junctions as continuous networks of adhesion strands are dependent on the membrane-associated scaffolding proteins ZO1 and ZO2. To understand how zona occludens (ZO) proteins organize junction assembly, we performed quantitative cell biology and in vitro reconstitution experiments. We discovered that ZO proteins self-organize membrane-attached compartments via phase separation. We identified the multivalent interactions of the conserved PDZ-SH3-GuK supra-domain as the driver of phase separation. These interactions are regulated by phosphorylation and intra-molecular binding. Formation of condensed ZO protein compartments is sufficient to specifically enrich and localize tight-junction proteins, including adhesion receptors, cytoskeletal adapters, and transcription factors. Our results suggest that an active-phase transition of ZO proteins into a condensed membrane-bound compartment drives claudin polymerization and coalescence of a continuous tight-junction belt.

DOI: 10.1016/j.cell.2019.10.011

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31127-4