9.B.213 The 7 TMS pH Sensor Rim21/PalH (Rim21/PalH) Family
External alkalization activates the Rim101 pathway in Saccharomyces cerevisiae. In this pathway, three integral membrane proteins, Rim21, Dfg16, and Rim9, are components of the pH sensor machinery. Obara et al. 2012 investigated the localization, physical interaction, and interrelationship of Rim21, Dfg16, and Rim9 and showed they form a complex in the plasma membrane in a patchy and mutually dependent manner. The Rim21 level was significantly decreased in dfg16Δ and rim9Δ cells. Upon external alkalization, the proteins were internalized and degraded. The transient degradation of Rim21 completely suppressed the Rim101 pathway but degradation of Dfg16 or Rim9 did not. Thius, Rim21 is the pH sensor protein and that Dfg16 and Rim9 play auxiliary roles by maintaining the level of Rim21 and assisting in its plasma membrane localization. Without external alkalization, the Rim101 pathway was activated in a Rim21-dependent manner by either protonophore treatment or depletion of phosphatidylserine in the inner leaflet of the plasma membrane, both of which caused plasma membrane depolarization like external alkalization. Therefore, plasma membrane depolarization seems to be one of the key signals for the pH sensor molecule Rim21 (Obara et al. 2012).
The C-terminal domain senses phospholipid asymmetry in the plasma membrane (Nishino et al. 2015). Plasma membrane (PM) lipid asymmetry and external alkalization are sensed by Rim21, which functions in the Rim101 pathway. Rim101 signaling is initiated at the PM by the recruitment of the Rim101 signaling complex. The PM physically associates with the cortical endoplasmic reticulum (ER) to form ER-PM contact sites, where several signaling events, lipid exchange, and ion transport take place. The Rim101 pathway is important for the adaptation to ER stress by compensating for alternations in PM lipid asymmetry induced by ER stress (Obara and Kihara 2016). The Rim21 protein in S. cerevisiae is called the PalH protein in Aspergillus nidulans