Phosphatidic acid modulation of Kv channel voltage sensor function

  1. Richard K Hite
  2. Joel A Butterwick
  3. Roderick MacKinnon  Is a corresponding author
  1. Howard Hughes Medical Institute, Rockefeller University, United States

Abstract

Membrane phospholipids can function as potent regulators of ion channel function. This study uncovers and investigates the effect of phosphatidic acid on Kv channel gating. Using the method of reconstitution into planar lipid bilayers, in which protein and lipid components are defined and controlled, we characterize two effects of phosphatidic acid. The first is a non-specific electrostatic influence on activation mediated by electric charge density on the extracellular and intracellular membrane surfaces. The second is specific to the presence of a primary phosphate group, acts only through the intracellular membrane leaflet and depends on the presence of a particular arginine residue in the voltage sensor. Intracellular phosphatidic acid accounts for a nearly 50 mV shift in the midpoint of the activation curve in a direction consistent with stabilization of the voltage sensor's closed conformation. These findings support a novel mechanism of voltage sensor regulation by the signaling lipid phosphatidic acid.

Article and author information

Author details

  1. Richard K Hite

    Howard Hughes Medical Institute, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Joel A Butterwick

    Howard Hughes Medical Institute, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Roderick MacKinnon

    Howard Hughes Medical Institute, Rockefeller University, New York, United States
    For correspondence
    mackinn@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Richard Aldrich, The University of Texas at Austin, United States

Version history

  1. Received: August 14, 2014
  2. Accepted: October 3, 2014
  3. Accepted Manuscript published: October 6, 2014 (version 1)
  4. Version of Record published: October 29, 2014 (version 2)

Copyright

© 2014, Hite et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Richard K Hite
  2. Joel A Butterwick
  3. Roderick MacKinnon
(2014)
Phosphatidic acid modulation of Kv channel voltage sensor function
eLife 3:e04366.
https://doi.org/10.7554/eLife.04366

Share this article

https://doi.org/10.7554/eLife.04366

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