| Title: | Plasma membrane aminoglycerolipid flippase function is required for signaling competence in the yeast mating pheromone response pathway |
| Author(s): | Sartorel E; Barrey E; Lau RK; Thorner J; |
| Address: | "Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3202. Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3202 jthorner@berkeley.edu" |
| ISSN/ISBN: | 1939-4586 (Electronic) 1059-1524 (Print) 1059-1524 (Linking) |
| Abstract: | "The class 4 P-type ATPases ('flippases') maintain membrane asymmetry by translocating phosphatidylethanolamine and phosphatidylserine from the outer leaflet to the cytosolic leaflet of the plasma membrane. In Saccharomyces cerevisiae, five related gene products (Dnf1, Dnf2, Dnf3, Drs2, and Neo1) are implicated in flipping of phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine. In MAT A: cells responding to alpha-factor, we found that Dnf1, Dnf2, and Dnf3, as well as the flippase-activating protein kinase Fpk1, localize at the projection ('shmoo') tip where polarized growth is occurring and where Ste5 (the central scaffold protein of the pheromone-initiated MAPK cascade) is recruited. Although viable, a MAT A: dnf1?Os dnf2?Os dnf3?Os triple mutant exhibited a marked decrease in its ability to respond to alpha-factor, which we could attribute to pronounced reduction in Ste5 stability resulting from an elevated rate of its Cln2?naCdc28-initiated degradation. Similarly, a MAT A: dnf1?Os dnf3?Os drs2?Os triple mutant also displayed marked reduction in its ability to respond to alpha-factor, which we could attribute to inefficient recruitment of Ste5 to the plasma membrane due to severe mislocalization of the cellular phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate pools. Thus proper remodeling of plasma membrane aminoglycerolipids and phosphoinositides is necessary for efficient recruitment, stability, and function of the pheromone signaling apparatus" |
| Keywords: | "ATP-Binding Cassette Transporters/genetics/*metabolism Adaptor Proteins, Signal Transducing/metabolism Adenosine Triphosphatases/genetics/*metabolism Calcium-Transporting ATPases/genetics Cell Membrane/*chemistry Pheromones/*physiology Phosphatidylinosito;" |
| Notes: | "MedlineSartorel, Elodie Barrey, Evelyne Lau, Rebecca K Thorner, Jeremy eng R01 GM021841/GM/NIGMS NIH HHS/ R01GM21841/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2014/11/08 Mol Biol Cell. 2015 Jan 1; 26(1):134-50. doi: 10.1091/mbc.E14-07-1193. Epub 2014 Nov 5" |
