近日，美国德克萨斯大学西南医学中心潘多加等研究人员合作发现，PI4P介导的固态Merlin凝聚体协调Hippo通路调控。相关论文于2024年8月9日发表在《科学》杂志上。

研究人员发现，肿瘤抑制因子Merlin，作为Hippo通路的上游调控因子，定位于果蝇上皮细胞的细胞连接和中间顶端皮质，其中后者形成固态凝聚体并激活Hippo信号通路。

Merlin的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的调节受到Pez和细胞骨架张力的拮抗性控制。

Merlin凝聚体的固态材料特性对于生理功能至关重要，并且保护凝聚体免受外部干扰。总的来说，这些发现揭示了固态凝聚体在正常生理中的重要作用，并揭示了其形成和解体的调控机制。

据悉，尽管最近的研究涉及液态生物大分子凝聚体在多种细胞过程中的作用，但许多生物大分子凝聚体存在于固态状态，其功能和调控机制尚不完全清楚。

附：英文原文

Title: PI4P-mediated solid-like Merlin condensates orchestrate Hippo pathway regulation

Author: Pengfei Guo, Bing Li, Wei Dong, Huabin Zhou, Li Wang, Ting Su, Christopher Carl, Yonggang Zheng, Yang Hong, Hua Deng, Duojia Pan

Issue&Volume: 2024-08-09

Abstract: 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.

DOI: adf4478

Source: https://www.science.org/doi/10.1126/science.adf4478