Department of Physiology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Science. 2024 Aug 9;385(6709):eadf4478. doi: 10.1126/science.adf4478.
Despite recent studies implicating liquid-like biomolecular condensates in diverse cellular processes, many biomolecular condensates exist in a solid-like state, and their function and regulation are less understood. We show that the tumor suppressor Merlin, an upstream regulator of the Hippo pathway, localizes to both cell junctions and medial apical cortex in epithelia, with the latter forming solid-like condensates that activate Hippo signaling. Merlin condensation required phosphatidylinositol-4-phosphate (PI4P)-mediated plasma membrane targeting and was antagonistically controlled by Pez and cytoskeletal tension through plasma membrane PI4P regulation. The solid-like material properties of Merlin condensates are essential for physiological function and protect the condensates against external perturbations. Collectively, these findings uncover an essential role for solid-like condensates in normal physiology and reveal regulatory mechanisms for their formation and disassembly.
尽管最近的研究表明液态生物分子凝聚物参与了多种细胞过程，但许多生物分子凝聚物仍处于固态，其功能和调节机制尚不清楚。我们发现肿瘤抑制因子 Merlin 是 Hippo 通路的上游调节剂，它在上皮细胞中定位于细胞连接和中部顶端皮质，后者形成固态凝聚物，激活 Hippo 信号通路。 Merlin 凝聚需要磷脂酰肌醇-4-磷酸（PI4P）介导的质膜靶向，并且通过质膜 PI4P 调节被 Pez 和细胞骨架张力拮抗控制。 Merlin 凝聚物的固态物质特性对于生理功能至关重要，并保护凝聚物免受外部干扰。总的来说，这些发现揭示了固态凝聚物在正常生理中的重要作用，并揭示了它们形成和分解的调节机制。
