Nature Cell Biology ( IF 17.3 ) Pub Date : 2022-06-16 , DOI: 10.1038/s41556-022-00936-6 Mao Zhang 1 , Cheng Zhu 2 , Yuanyuan Duan 1 , Tongbao Liu 3 , Haoping Liu 4 , Chang Su 1 , Yang Lu 1
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 CO2 concentrations is critical for all organisms. Conversion of CO2 to HCO3− by carbonic anhydrase and subsequent HCO3−-triggered signalling are thought to be important for cellular responses to CO2 (refs. 1,2,3). However, carbonic anhydrases are suggested to transduce a change in CO2 rather than be a direct CO2 sensor4,5, the mechanism(s) by which organisms sense CO2 remain unknown. Here we demonstrate that a unique group of PP2C phosphatases from fungi and plants senses CO2, but not HCO3−, 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 CO2 in an IDR-dependent manner. The IDRs in PP2Cs are characterized by a sequence of polar amino acids enriched in serine/threonine, which provides CO2 responsiveness. CO2-responsive activation of PP2Cs via the serine/threonine-rich IDR-mediated phase separation represents a direct CO2 sensing mechanism and is widely exploited.
中文翻译:
PP2C 磷酸酶的内在无序区域可作为保守的 CO2 传感器
二氧化碳不仅在碳循环中起着核心作用,而且在活细胞中也起着至关重要的作用。适应不断变化的 CO 2浓度对所有生物都至关重要。通过碳酸酐酶将CO 2转化为HCO 3 -和随后的HCO 3 -触发信号被认为对于细胞对CO 2的反应很重要(参考文献1,2,3)。然而,建议碳酸酐酶转导 CO 2 的变化,而不是直接的 CO 2传感器4,5,这是生物体感知 CO 2的机制仍然未知。在这里,我们证明了来自真菌和植物的一组独特的 PP2C 磷酸酶可以感知 CO 2,但不感知 HCO 3 -,以控制不同的细胞程序。与其他磷酸酶不同,这些 PP2Cs 都具有内在无序区域 (IDR)。它们在细胞和体外通过相分离形成可逆的液体状液滴,并以 IDR 依赖性方式响应升高的环境 CO 2被激活。PP2Cs 中的 IDR 以富含丝氨酸/苏氨酸的极性氨基酸序列为特征,提供 CO 2响应性。通过富含丝氨酸/苏氨酸的 IDR 介导的相分离对 PP2C 的CO 2响应性激活代表了直接的 CO2传感机制,并被广泛利用。