Ehg1/May24 stabilizes yeast amino acid permease by facilitating its localization to lipid rafts under high hydrostatic pressure.

Pressure is a thermodynamic parameter that influences chemical equilibrium and reaction kinetics; however, its effects on complex cellular mechanisms remain largely unexplored. In this study, we investigated the role of Ehg1 (also known as May24), a novel endoplasmic reticulum (ER) membrane protein in Saccharomyces cerevisiae, in the stabilization of tryptophan permease Tat2, which ensures cell growth under high hydrostatic pressure (∼25 MPa, megapascals). We show that Ehg1 in the cortical ER (cER) physically interacts with the plasma membrane Tat2 in trans and plays a vital role in preserving its localization in the plasma membrane by facilitating its partitioning into the plasma membrane microdomains, lipid rafts. This stabilization depends on the contact between the cER and plasma membrane, which is critical for effective nutrient transport under pressure, as evidenced from the fact that Tat2 was destabilized in Δtether and Δ-super-tether strains lacking such contact. These insights into the regulation of nutrient permease under high pressure contribute to our understanding of microbial adaptation to extreme environments.