An ER membrane protein, Sop4, facilitates ER export of the yeast plasma membrane [H+]ATPase, Pma1.

We have analyzed the mechanism by which Sop4, a novel ER membrane protein, regulates quality control and intracellular transport of Pma1-7, a mutant plasma membrane ATPase. At the restrictive temperature, newly synthesized Pma1-7 is targeted for vacuolar degradation instead of being correctly delivered to the cell surface. Loss of Sop4 at least partially corrects vacuolar mislocalization, allowing Pma1-7 routing to the plasma membrane. Ste2-3 is a mutant pheromone receptor which, like Pma1-7, is defective in targeting to the cell surface, resulting in a mating defect. sop4delta suppresses the mating defect of ste2-3 cells as well as the growth defect of pma1-7. Visualization of newly synthesized Pma1-7 in sop4delta cells by indirect immunofluorescence reveals delayed export from the ER. Similarly, ER export of wild-type Pma1 is delayed in the absence of Sop4 although intracellular transport of Gas1 and CPY is unaffected. These observations suggest a model in which a selective increase in ER residence time for Pma1-7 may allow it to achieve a more favorable conformation for subsequent delivery to the plasma membrane. In support of this model, newly synthesized Pma1-7 is also routed to the plasma membrane upon release from a general block of ER-to-Golgi transport in sec13-1 cells.