Phosphatidylinositol-3,5-bisphosphate: metabolism and physiological functions.

Phosphatidylinositol (PtdIns) is a membrane phospholipid composed of diacylglycerol and a D-myo-inositol head group. In mammals, the hydroxyl groups at the D3, D4 and D5 positions of the inositol ring can be phosphorylated to yield seven phosphoinositide derivatives. PtdIns-3,5-bisphosphate [PtdIns(3,5)P2] is the most recently discovered species of phosphoinositide that is generated by the phosphorylation of PtdIns(3)P at the D5 position by PtdIns phosphate kinase and catabolized through the dephosphorylation by myotubularin family of phosphatases. Genetic and biochemical analyses of the enzymes metabolizing PtdIns(3,5)P2 have revealed that this phospholipid is involved in the control of endolysosomal systems and plays crucial roles in various mammalian tissues. In this article, we review the current state of knowledge of the metabolic/physiological functions of PtdIns(3,5)P2, and describe how disruption of these functions may contribute to human diseases.