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PI4P-mediated solid-like Merlin condensates orchestrate Hippo pathway regulation
Science ( IF 44.7 ) Pub Date : 2024-08-08 , DOI: 10.1126/science.adf4478
Pengfei Guo 1 , Bing Li 1 , Wei Dong 2 , Huabin Zhou 3 , Li Wang 1 , Ting Su 1 , Christopher Carl 1 , Yonggang Zheng 1 , Yang Hong 2 , Hua Deng 1 , Duojia Pan 1
Affiliation  

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 Drosophila 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.

中文翻译:


PI4P介导的类固体Merlin凝聚物协调Hippo通路调节



尽管最近的研究表明多种细胞过程中存在类液体生物分子凝聚体,但许多生物分子凝聚体以类固体状态存在,并且它们的功能和调节知之甚少。我们发现肿瘤抑制因子 Merlin 是 Hippo 通路的上游调节因子,定位于果蝇上皮细胞的细胞连接处和内侧顶皮层,后者形成激活 Hippo 信号传导的固体状凝聚物。 Merlin 缩合需要 4-磷酸磷脂酰肌醇 (PI4P) 介导的质膜靶向,并通过质膜 PI4P 调节受到 Pez 和细胞骨架张力的拮抗控制。 Merlin 凝聚物的类固体材料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,这些发现揭示了类固体凝聚物在正常生理学中的重要作用,并揭示了其形成和分解的调节机制。
更新日期:2024-08-08
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