The Saccharomyces cerevisiae protein Kes1/Osh4 is a member of the enigmatic family of oxysterol binding proteins found throughout Eukarya united by a beta-barrel structure that binds sterols and oxysterols. In this study, we determine that phosphoinositides are the major determinant in membranes that faciliate Kes1 association both in vitro and in cells. Increased expression of Kes1 in yeast cells decreased the level of both phosphatidylinositol-4-phosphate (PI-4P) and phosphatidylinositol-3-phosphate (PI-3P). Phosphoinositide and sterol binding by Kes1 were necessary for Kes1 to decrease the level of PI-4P but not PI-3P. Kes1 inhibited vesicular trafficking between the trans-Golgi and plasma membrane as evidenced by accumulation of the v-SNARE Snc1 in the cytoplasmic vesicles. Sterol and phosphoinositide binding by Kes1 both contributed to its regulation of Snc1 trafficking. This study also describes a previously unknown role for Kes1 in regulation of the autophagy/cytoplasm to vacuole trafficking pathway. The Kes1 mediated regulation of the autophagy/ cytoplasm to vacuole trafficking pathway was prevented by increasing expression of the PI 3-kinase Vps34, suggesting that it is the Kes1 mediated decrease in PI-3P level that contributes to this regulation.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|