KES1P SHARES HOMOLOGY WITH HUMAN OXYSTEROL BINDING-PROTEIN AND PARTICIPATES IN A NOVEL REGULATORY PATHWAY FOR YEAST GOLGI-DERIVED TRANSPORTVESICLE BIOGENESIS

The yeast phosphatidylinositol transfer protein (Sec14p) is required f or biogenesis of Golgi-derived transport vesicles and cell viability, and this essential Sec14p requirement is abrogated by inactivation of the CDP-choline pathway for phosphatidylcholine biosynthesis. These fi ndings indicate that Sec14p functions to alleviate a CDP-choline pathw ay-mediated toxicity to yeast Golgi secretory function, We now report that this toxicity is manifested through the action of yeast Kes1p, a polypeptide that shares homology with the ligand-binding domain of hum an oxysterol binding protein (OSBP), Identification of Kes1p as a nega tive effector for Golgi function provides the first direct insight int o the biological role of any member of the OSBP family, and describes a novel pathway for the regulation of Golgi-derived transport vesicle biogenesis.