Regulation of KCNQ/Kv7 family voltage-gated K + channels by lipids

Biochim Biophys Acta Biomembr. 2017 Apr;1859(4):586-597. doi: 10.1016/j.bbamem.2016.10.023. Epub 2016 Nov 4.

Abstract

Many years of studies have established that lipids can impact membrane protein structure and function through bulk membrane effects, by direct but transient annular interactions with the bilayer-exposed surface of protein transmembrane domains, and by specific binding to protein sites. Here, we focus on how phosphatidylinositol 4,5-bisphosphate (PIP2) and polyunsaturated fatty acids (PUFAs) impact ion channel function and how the structural details of the interactions of these lipids with ion channels are beginning to emerge. We focus on the Kv7 (KCNQ) subfamily of voltage-gated K+ channels, which are regulated by both PIP2 and PUFAs and play a variety of important roles in human health and disease. This article is part of a Special Issue entitled: Lipid order/lipid defects and lipid-control of protein activity edited by Dirk Schneider.

Keywords: Annular; Channel; KCNQ1; Kv7.1; Lipids; Membrane; PIP2; PUFA; Potassium; Voltage-gated.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Epilepsy, Benign Neonatal / metabolism*
  • Epilepsy, Benign Neonatal / pathology
  • Fatty Acids, Unsaturated / chemistry
  • Fatty Acids, Unsaturated / metabolism
  • Hearing Loss, Bilateral / metabolism*
  • Hearing Loss, Bilateral / pathology
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • KCNQ1 Potassium Channel / chemistry*
  • KCNQ1 Potassium Channel / deficiency
  • KCNQ1 Potassium Channel / metabolism
  • Long QT Syndrome / metabolism*
  • Long QT Syndrome / pathology
  • Membrane Lipids / chemistry*
  • Membrane Lipids / metabolism
  • Models, Molecular
  • Phosphatidylinositol 4,5-Diphosphate / chemistry
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / deficiency
  • Protein Isoforms / metabolism
  • Protein Structure, Secondary

Substances

  • Fatty Acids, Unsaturated
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Membrane Lipids
  • Phosphatidylinositol 4,5-Diphosphate
  • Protein Isoforms