Zhang Mao, Zhu Cheng, Duan Yuanyuan, Liu Tongbao, Liu Haoping, Su Chang, Lu Yang
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, School of Life Sciences, Tianjin University, Tianjin, China.
Nat Cell Biol. 2022 Jul;24(7):1029-1037. doi: 10.1038/s41556-022-00936-6. Epub 2022 Jun 16.
Carbon dioxide not only plays a central role in the carbon cycle, but also acts as a crucial signal in living cells. Adaptation to changing CO concentrations is critical for all organisms. Conversion of CO to HCO by carbonic anhydrase and subsequent HCO-triggered signalling are thought to be important for cellular responses to CO (refs. ). However, carbonic anhydrases are suggested to transduce a change in CO rather than be a direct CO sensor, the mechanism(s) by which organisms sense CO remain unknown. Here we demonstrate that a unique group of PP2C phosphatases from fungi and plants senses CO, but not HCO, to control diverse cellular programmes. Different from other phosphatases, these PP2Cs all have an intrinsically disordered region (IDR). They formed reversible liquid-like droplets through phase separation both in cells and in vitro, and were activated in response to elevated environmental CO in an IDR-dependent manner. The IDRs in PP2Cs are characterized by a sequence of polar amino acids enriched in serine/threonine, which provides CO responsiveness. CO-responsive activation of PP2Cs via the serine/threonine-rich IDR-mediated phase separation represents a direct CO sensing mechanism and is widely exploited.
二氧化碳不仅在碳循环中起着核心作用，而且在活细胞中充当关键信号。适应不断变化的二氧化碳浓度对所有生物体都至关重要。碳酸酐酶将二氧化碳转化为碳酸氢根以及随后由碳酸氢根触发的信号传导被认为对细胞对二氧化碳的反应很重要（参考文献）。然而，有人提出碳酸酐酶传导的是二氧化碳的变化而非直接作为二氧化碳传感器，生物体感知二氧化碳的机制仍然未知。在这里，我们证明来自真菌和植物的一组独特的PP2C磷酸酶能够感知二氧化碳而非碳酸氢根，以控制多种细胞程序。与其他磷酸酶不同，这些PP2C都有一个内在无序区域（IDR）。它们在细胞内和体外均通过相分离形成可逆的类液滴，并以依赖IDR的方式响应环境中升高的二氧化碳而被激活。PP2C中的IDR以富含丝氨酸/苏氨酸的极性氨基酸序列为特征，这赋予了对二氧化碳的响应性。通过富含丝氨酸/苏氨酸的IDR介导的相分离实现的PP2C对二氧化碳的响应性激活代表了一种直接的二氧化碳传感机制，并且被广泛利用。
