title: Phosphoinositide control of membrane protein function: a frontier led by studies on ion channels.
abstract: Anionic phospholipids are critical constituents of the inner leaflet of the plasma membrane, ensuring appropriate membrane topology of transmembrane proteins. Additionally, in eukaryotes, the negatively charged phosphoinositides serve as key signals not only through their hydrolysis products but also through direct control of transmembrane protein function. Direct phosphoinositide control of the activity of ion channels and transporters has been the most convincing case of the critical importance of phospholipid-protein interactions in the functional control of membrane proteins. Furthermore, second messengers, such as [Ca(2+)]i, or posttranslational modifications, such as phosphorylation, can directly or allosterically fine-tune phospholipid-protein interactions and modulate activity. Recent advances in structure determination of membrane proteins have allowed investigators to obtain complexes of ion channels with phosphoinositides and to use computational and experimental approaches to probe the dynamic mechanisms by which lipid-protein interactions control active and inactive protein states.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, Virginia 23298-0551; email: delogothetis@vcu.edu.
authors.forename: Diomedes E
authors.initials: DE
authors.lastname: Logothetis
authors.forename: Vasileios I
authors.initials: VI
authors.lastname: Petrou
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.forename: Rahul
authors.initials: R
authors.lastname: Mahajan
authors.forename: Xuan-Yu
authors.initials: XY
authors.lastname: Meng
authors.forename: Scott K
authors.initials: SK
authors.lastname: Adney
authors.forename: Meng
authors.initials: M
authors.lastname: Cui
authors.forename: Lia
authors.initials: L
authors.lastname: Baki
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D010716:Phosphatidylinositols / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins; D010716:Phosphatidylinositols
keywords: P2; P2-induced gating; PI(4,5); ion channels; modulation; phosphoinositides; phosphorylation