title: Phosphatidylinositol 3,5-bisphosphate: metabolism and cellular functions.
abstract: Polyphosphoinositides (PPIn) are low-abundance membrane phospholipids that each bind to a distinctive set of effector proteins and, thereby, regulate a characteristic suite of cellular processes. Major functions of phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P(2)] are in membrane and protein trafficking, and in pH control in the endosome-lysosome axis. Recently identified PtdIns(3,5)P(2) effectors include a family of novel beta-propeller proteins, for which we propose the name PROPPINs [for beta-propeller(s) that binds PPIn], and possibly proteins of the epsin and CHMP (charged multi-vesicular body proteins) families. All eukaryotes, with the exception of some pathogenic protists and microsporidians, possess proteins needed for the formation, metabolism and functions of PtdIns(3,5)P(2). The importance of PtdIns(3,5)P(2) for normal cell function is underscored by recent evidence for its involvement in mammalian cell responses to insulin and for PtdIns(3,5)P(2) dysfunction in the human genetic conditions X-linked myotubular myopathy, Type-4B Charcot-Marie-Tooth disease and fleck corneal dystrophy.
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK. r.h.michell@bham.ac.uk
authors.forename: Robert H
authors.initials: RH
authors.lastname: Michell
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Heath
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lemmon
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Dove
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016384:Consensus Sequence; D008322:Mammals; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport
chemical_list: D018129:Phosphatidylinositol Phosphates; C106336:phosphatidylinositol 3,5-diphosphate; D019869:Phosphatidylinositol 3-Kinases