Novel role of the phosphatidylinositol phosphatase Sac1 in membrane homeostasis and polarized growth in Candida albicans.

Phosphoinositides (PIPs) are one kind of membrane components functioning in many intracellular processes, especially in signaling transduction and membrane transport. Phosphatidylinositide phosphatases (PIPases) are specifically important for the PIP homeostasis in cell. In our previous study, we have identified the actin-related protein CaSac1 in Candida albicans, while its functional mechanisms in regulating membrane homeostasis has not been identified. Here, we show that the PIPase CaSac1 is a main membrane-related protein and regulates hyphal polarization by governing phosphoinositide dynamic and plasma membrane (PM) electrostatic field. Deletion of CaSAC1 resulted in large-scale abnormal redistribution of phosphatidylinositide 4-phosphate (PI4P) from the endomembrane to the PM. This abnormality further led to disturbance of the PM's negative electrostatic field and abnormally spotted distribution of phosphatidylinositide 4,5-bisphosphate (PI(4,5)P). These changes led to a severe defect in polarized hyphal growth, which could be diminished with recovery of the PM's negative electrostatic field by the anionic polymer polyacrylic acid (PAA). This study revealed that the PIPase CaSac1 plays an essential role in regulating membrane homeostasis and membrane traffic, contributing to establishment of polarized hyphal growth.