Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Scripps Institution of Oceanography, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Proc Biol Sci. 2017 Nov 15;284(1866). doi: 10.1098/rspb.2017.1769.
Maintaining stable intracellular pH (pHi) is essential for homeostasis, and requires the ability to both sense pH changes that may result from internal and external sources, and to regulate downstream compensatory pH pathways. Here we identified the cAMP-producing enzyme soluble adenylyl cyclase (sAC) as the first molecular pH sensor in corals. sAC protein was detected throughout coral tissues, including those involved in symbiosis and calcification. Application of a sAC-specific inhibitor caused significant and reversible pHi acidosis in isolated coral cells under both dark and light conditions, indicating sAC is essential for sensing and regulating pHi perturbations caused by respiration and photosynthesis. Furthermore, pHi regulation during external acidification was also dependent on sAC activity. Thus, sAC is a sensor and regulator of pH disturbances from both metabolic and external origin in corals. Since sAC is present in all coral cell types, and the cAMP pathway can regulate virtually every aspect of cell physiology through post-translational modifications of proteins, sAC is likely to trigger multiple homeostatic mechanisms in response to pH disturbances. This is also the first evidence that sAC modulates pHi in any non-mammalian animal. Since corals are basal metazoans, our results indicate this function is evolutionarily conserved across animals.
维持稳定的细胞内 pH（pHi）对于体内平衡至关重要，这需要既能感知可能由内部和外部来源引起的 pH 变化，又能调节下游补偿 pH 途径的能力。在这里，我们将产生 cAMP 的酶可溶性腺苷酸环化酶（sAC）鉴定为珊瑚中的第一个分子 pH 传感器。sAC 蛋白在珊瑚组织中均有检测到，包括参与共生和钙化的组织。在黑暗和光照条件下，sAC 特异性抑制剂的应用可导致分离的珊瑚细胞中显著且可逆的 pHi 酸中毒，表明 sAC 对于由呼吸和光合作用引起的 pHi 扰动的感应和调节至关重要。此外，外部酸化过程中的 pHi 调节也依赖于 sAC 活性。因此，sAC 是珊瑚中代谢和外部来源引起的 pH 干扰的传感器和调节剂。由于 sAC 存在于所有珊瑚细胞类型中，并且 cAMP 途径可以通过蛋白质的翻译后修饰来调节细胞生理学的几乎所有方面，因此 sAC 可能会触发多种针对 pH 干扰的稳态机制。这也是 sAC 调节任何非哺乳动物动物 pHi 的第一个证据。由于珊瑚是基础后生动物，我们的研究结果表明，该功能在动物中是进化保守的。
