多相合并介导Hippo途径的激活

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,多相合并介导Hippo途径的激活。相关论文于2022年10月31日在线发表于国际学术期刊《细胞》。

研究人员表明,Hippo信号通路的上游调节器形成了功能拮抗的凝集物,它们凝聚成一个共同的相,提供了一种在没有凝集物溶解的情况下抵消生物分子凝集物功能的模式。具体来说,负调节器SLMAP形成Hippo失活凝集物,从而促进STRIPAK复合物对途径的抑制。在对细胞-细胞接触或渗透压的反应中,正调节器AMOT和KIBRA形成Hippo激活凝集物来促进途径的激活。

功能上拮抗的SLMAP和AMOT/KIBRA凝集物进一步合并成一个共同的相,从而抑制STRIPAK的功能。这些发现为限制生物分子凝集物的活性而不溶解凝集物提供了一个范例,阐明了多相组织的分子原理,并为理解Hippo信号通路的上游调节提供了一个概念框架。

据介绍,生物分子凝集物的功能往往受到凝集物溶解的限制。凝集物是否可以在没有凝集物溶解的情况下被抑制还不清楚。

附:英文原文

Title: Multiphase coalescence mediates Hippo pathway activation

Author: Li Wang, Kyungsuk Choi, Ting Su, Bing Li, Xiaofeng Wu, Ruihui Zhang, Jordan H. Driskill, Hongde Li, Huiyan Lei, Pengfei Guo, Elizabeth H. Chen, Yonggang Zheng, Duojia Pan

Issue&Volume: 2022-10-31

Abstract: The function of biomolecular condensates is often restricted by condensate dissolution.Whether condensates can be suppressed without condensate dissolution is unclear. Here,we show that upstream regulators of the Hippo signaling pathway form functionallyantagonizing condensates, and their coalescence into a common phase provides a modeof counteracting the function of biomolecular condensates without condensate dissolution.Specifically, the negative regulator SLMAP forms Hippo-inactivating condensates tofacilitate pathway inhibition by the STRIPAK complex. In response to cell-cell contactor osmotic stress, the positive regulators AMOT and KIBRA form Hippo-activating condensatesto facilitate pathway activation. The functionally antagonizing SLMAP and AMOT/KIBRAcondensates further coalesce into a common phase to inhibit STRIPAK function. Thesefindings provide a paradigm for restricting the activity of biomolecular condensateswithout condensate dissolution, shed light on the molecular principles of multiphaseorganization, and offer a conceptual framework for understanding upstream regulationof the Hippo signaling pathway.

DOI: 10.1016/j.cell.2022.09.036

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01255-7

来源:科学网  小柯机器人