Yeast cells adapt to alkaline conditions by activating the Rim101 alkali-responsive pathway. Rim21 acts as a sensor in the Rim101 pathway and detects extracellular alkalization. Interestingly, Rim21 is also known to be activated by alterations involving the lipid asymmetry of the plasma membrane. In this study, we briefly summarize the mechanism of activation and the signal transduction cascade of the Rim101 pathway and propose a hypothesis on how Rim21 is able to detect distinct signals, particularly external alkalization, and altered lipid asymmetry. We found that external alkalization can suppress transbilayer movements of phospholipids between the two leaflets of the plasma membrane, which may lead to the disturbance of the lipid asymmetry of the plasma membrane. Therefore, we propose that external alteration is at least partly sensed by Rim21 through alterations in lipid asymmetry. Understanding this activation mechanism could greatly contribute to drug development against fungal infections.

酵母细胞通过激活 Rim101 碱响应途径来适应碱性条件。Rim21 在 Rim101 通路中充当传感器并检测细胞外碱化。有趣的是，还已知 Rim21 被涉及质膜脂质不对称性的改变激活。在这项研究中，我们简要总结了 Rim101 通路的激活机制和信号转导级联，并提出了一个关于 Rim21 如何能够检测不同信号，特别是外部碱化和脂质不对称改变的假设。我们发现外部碱化可以抑制磷脂在质膜两个小叶之间的跨双层运动，这可能导致质膜脂质不对称性的紊乱。所以，我们提出，Rim21 通过脂质不对称的改变至少部分地感知到外部改变。了解这种激活机制可以极大地促进针对真菌感染的药物开发。