Mesh : Animals Cell Membrane / metabolism Drosophila melanogaster / metabolism genetics Drosophila Proteins / metabolism genetics Intercellular Junctions / metabolism Intracellular Signaling Peptides and Proteins / metabolism genetics Neurofibromin 2 / metabolism genetics Phosphatidylinositol Phosphates / metabolism Protein Serine-Threonine Kinases / metabolism Hippo Signaling Pathway Biomolecular Condensates / metabolism

来  源:   DOI:10.1126/science.adf4478

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.
摘要:
尽管最近的研究暗示液体状生物分子冷凝物在不同的细胞过程中,许多生物分子缩合物以固态存在,它们的功能和调节很少被理解。我们证明肿瘤抑制因子Merlin,河马通路的上游调节因子,定位于果蝇上皮的细胞连接和内侧顶端皮质,后者形成激活Hippo信号的固体状凝聚物。Merlin缩合需要磷脂酰肌醇-4-磷酸(PI4P)介导的质膜靶向,并且通过质膜PI4P调节受到Pez和细胞骨架张力的拮抗控制。Merlin冷凝物的固体状材料特性对于生理功能至关重要,并保护冷凝物免受外部扰动。总的来说,这些发现揭示了固体状冷凝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。
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