Plasma membrane aminoglycerolipid flippase function is required for signaling competence in the yeast mating pheromone response pathway

摘要: The class 4 P-type ATPases ("flippases") maintain membrane asymmetry by translocating phosphatidylethanolamine and phosphatidylserine from the outer leaflet to cytosolic of plasma membrane. In Saccharomyces cerevisiae, five related gene products (Dnf1, Dnf2, Dnf3, Drs2, Neo1) are implicated in flipping phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine. MAT A: cells responding α-factor, we found that Dnf1, as well flippase-activating protein kinase Fpk1, localize at projection ("shmoo") tip where polarized growth is occurring Ste5 (the central scaffold pheromone-initiated MAPK cascade) recruited. Although viable, a dnf1∆ dnf2∆ dnf3∆ triple mutant exhibited marked decrease its ability respond which could attribute pronounced reduction stability resulting an elevated rate Cln2⋅Cdc28-initiated degradation. Similarly, drs2∆ also displayed inefficient recruitment due severe mislocalization cellular phosphatidylinositol 4-phosphate 4,5-bisphosphate pools. Thus proper remodeling aminoglycerolipids phosphoinositides necessary for efficient recruitment, stability, function pheromone signaling apparatus.