The Rim101 pathway mediates adaptation to external alkalization and altered lipid asymmetry: hypothesis describing the detection of distinct stresses by the Rim21 sensor protein.

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.