title: Phosphatidylinositol-3,5-bisphosphate: metabolism and physiological functions.
abstract: 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.
authors.affiliation: Department of Medical Biology, Akita University Graduate School of Medicine, Akita 010-8543, Japan. takasuga@med.akita-u.ac.jp
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Takasuga
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010766:Phosphorylation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018129:Phosphatidylinositol Phosphates; C106336:phosphatidylinositol 3,5-diphosphate; C055525:phosphatidylinositol 3-phosphate; C113567:phosphatidylinositol 5-phosphate; D019869:Phosphatidylinositol 3-Kinases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin
keywords: Fig4; PIKfyve; PipkIII; Sac3; phosphatidylinositol-3,5-bisphosphate