Phosphatidic acid modulation of Kv channel voltage sensor function

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...

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Autores principales: Hite, Richard K, Butterwick, Joel A, MacKinnon, Roderick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212207/
https://www.ncbi.nlm.nih.gov/pubmed/25285449
http://dx.doi.org/10.7554/eLife.04366
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author Hite, Richard K
Butterwick, Joel A
MacKinnon, Roderick
author_facet Hite, Richard K
Butterwick, Joel A
MacKinnon, Roderick
author_sort Hite, Richard K
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.04366.001
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spelling pubmed-42122072014-11-21 Phosphatidic acid modulation of Kv channel voltage sensor function Hite, Richard K Butterwick, Joel A MacKinnon, Roderick eLife Biophysics and Structural Biology 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. DOI: http://dx.doi.org/10.7554/eLife.04366.001 eLife Sciences Publications, Ltd 2014-10-06 /pmc/articles/PMC4212207/ /pubmed/25285449 http://dx.doi.org/10.7554/eLife.04366 Text en Copyright © 2014, Hite et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biophysics and Structural Biology
Hite, Richard K
Butterwick, Joel A
MacKinnon, Roderick
Phosphatidic acid modulation of Kv channel voltage sensor function
title Phosphatidic acid modulation of Kv channel voltage sensor function
title_full Phosphatidic acid modulation of Kv channel voltage sensor function
title_fullStr Phosphatidic acid modulation of Kv channel voltage sensor function
title_full_unstemmed Phosphatidic acid modulation of Kv channel voltage sensor function
title_short Phosphatidic acid modulation of Kv channel voltage sensor function
title_sort phosphatidic acid modulation of kv channel voltage sensor function
topic Biophysics and Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212207/
https://www.ncbi.nlm.nih.gov/pubmed/25285449
http://dx.doi.org/10.7554/eLife.04366
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