紧密连接
生物
细胞生物学
细胞骨架
电池极性
PDZ域
克洛丹
支架蛋白
膜蛋白
细胞粘附
封堵器
生物物理学
细胞结
膜
细胞
信号转导
生物化学
作者
Oliver Beutel,Riccardo Maraspini,Karina Pombo‐García,Cécilie Martin-Lemaitre,Alf Honigmann
出处
期刊:Cell
[Elsevier]
日期:2019-10-01
卷期号:179 (4): 923-936.e11
被引量:287
标识
DOI:10.1016/j.cell.2019.10.011
摘要
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.
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