The phosphoinositide phosphatase Sac1p controls trafficking of the yeast Chs3p chitin synthase

Phosphoinositide phosphatases play an essential but as yet not well-underst ood role in lipid-based signal transduction. Members of a subfamily of thes e enzymes share a specific domain that was first identified in the yeast Sa c1 protein [1]. Sac1 homology domains were shown to exhibit 3- and 4-phosph atase activity in vitro [2, 3] and were also found, in addition to rat and yeast Sac1p, in yeast Inp/Sjl proteins [4, 5] and mammalian synaptojanins [ 6]. Despite the detailed in vitro characterization of the enzymatic propert ies of yeast Sac1p, the exact cellular function of this protein has remaine d obscure. We report here that Sac1p has a specific role in secretion and a cts as an antagonist of the phosphatidylinositol 4-kinase Pik1p in Golgi tr afficking. Elimination of Sac1p leads to excessive forward transport of chi tin synthases and thus causes specific cell wall defects. Similar defects i n membrane trafficking are caused by the overexpression of PIK1. Taken toge ther, these findings provide strong evidence that the generation of Ptdlns( 4)P is sufficient to trigger forward transport from the Golgi to the plasma membrane and that Sac1p is critically required for the termination of this signal.