Roles of lipids in Golgi sorting

The addition of carbohydrate moieties to biosynthetic cargo in the Golgi apparatus is carried out by glycosyltransferases that function sequentially, such that the products of early acting enzymes are substrates for later‐acting enzymes. The location of enzymes within the Golgi stack parallels the glycosylation reactions; early‐acting enzymes are enriched in cis/medial Golgi compartments while later‐acting enzymes are enriched in medial/trans compartments. Phosphatidylinositol 4‐kinases (PI4Ks) are key regulators of the sorting reactions that are required to establish and maintain the structure and function of the Golgi. We have identified factors and pathways in yeast that mediate PI4K signaling to mediate retention of Golgi enzymes. One factor is Vps74, a peripheral Golgi membrane protein that is the ortholog of human GOLPH3, whose over‐expression has been correlated with activation of mTOR and oncogenic transformation. Genetic interaction studies have led to the identification of additional factors that function with PI4K and Vps74 to maintain the proper identity of Golgi compartments.