Phase separation as a therapeutic target in tight junction-associated human diseases.

Acta Pharmacologica Sinica
Shuang Sun, Jun Zhou

Abstract

Tight junctions (TJs) play an important role in the maintenance of epithelial and endothelial barriers. Zonula occludens (ZO) proteins are scaffolding molecules essential for the formation of TJ complexes, and abnormalities in ZO proteins have been implicated in various TJ-associated human diseases such as tumor invasion and metastasis, and barrier dysfunction. Recent studies reveal that liquid-liquid phase separation of ZO proteins drives the polymerization of TJ proteins into a continuous belt, which then recruits various proteins to form the TJ complex to regulate selective paracellular permeability and signal transduction. Herein, we describe recent advances on how ZO phase separation contributes to TJ formation and discuss the potential of phase separation as a target for the treatment of TJ-associated diseases.

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Citations

Oct 19, 2020·Journal of Clinical Laboratory Analysis·Manxi ZhengMin Liu
Jan 15, 2021·Drug Discovery Today·Sunil Kumar DubeyPrashant Kesharwani
Jan 19, 2021·Advanced Healthcare Materials·Lingyu FengJianlei Shen
May 21, 2021·Journal of Agricultural and Food Chemistry·Aobai TuYuanyuan Shan
Apr 30, 2021·Journal of Molecular Cell Biology·Hazrat IsmailXuebiao Yao

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