Beyond voltage-gated ion channels: Voltage-operated membrane proteins and cellular processes

J Cell Physiol. 2018 Oct;233(10):6377-6385. doi: 10.1002/jcp.26555. Epub 2018 Apr 18.

Abstract

Voltage-gated ion channels were believed to be the only voltage-sensitive proteins in excitable (and some non-excitable) cells for a long time. Emerging evidence indicates that the voltage-operated model is shared by some other transmembrane proteins expressed in both excitable and non-excitable cells. In this review, we summarize current knowledge about voltage-operated proteins, which are not classic voltage-gated ion channels as well as the voltage-dependent processes in cells for which single voltage-sensitive proteins have yet to be identified. Particularly, we will focus on the following. (1) Voltage-sensitive phosphoinositide phosphatases (VSP) with four transmembrane segments homologous to the voltage sensor domain (VSD) of voltage-gated ion channels; VSPs are the first family of proteins, other than the voltage-gated ion channels, for which there is sufficient evidence for the existence of the VSD domain; (2) Voltage-gated proton channels comprising of a single voltage-sensing domain and lacking an identified pore domain; (3) G protein coupled receptors (GPCRs) that mediate the depolarization-evoked potentiation of Ca2+ mobilization; (4) Plasma membrane (PM) depolarization-induced but Ca2+ -independent exocytosis in neurons. (5) Voltage-dependent metabolism of phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P2 , PIP2 ) in the PM. These recent discoveries expand our understanding of voltage-operated processes within cellular membranes.

Keywords: CIVDS; Ci-VSP; GPCRs; Hv1/VSOP; PtdIns(4,5)P2 metabolism; membrane potential.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acid Sensing Ion Channels / genetics
  • Animals
  • Cell Physiological Phenomena / genetics*
  • Exocytosis / genetics
  • Humans
  • Ion Channel Gating / genetics*
  • Ion Channel Gating / physiology
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Membrane Proteins / genetics*
  • Neurons / metabolism
  • Phosphatidylinositol 4,5-Diphosphate / genetics
  • Phosphoinositide Phosphatases / genetics*
  • Protein Domains / genetics

Substances

  • Acid Sensing Ion Channels
  • Ion Channels
  • Membrane Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphoinositide Phosphatases