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Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains

K(2P)2.1 (TREK-1) is a polymodal two-pore domain leak potassium channel that responds to external pH, GPCR-mediated phosphorylation signals, and temperature through the action of distinct sensors within the channel. How the various intracellular and extracellular sensory elements control channel fun...

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Autores principales: Bagriantsev, Sviatoslav N, Clark, Kimberly A, Minor, Daniel L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Molecular Biology Organization 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411076/
https://www.ncbi.nlm.nih.gov/pubmed/22728824
http://dx.doi.org/10.1038/emboj.2012.171
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author Bagriantsev, Sviatoslav N
Clark, Kimberly A
Minor, Daniel L
author_facet Bagriantsev, Sviatoslav N
Clark, Kimberly A
Minor, Daniel L
author_sort Bagriantsev, Sviatoslav N
collection PubMed
description K(2P)2.1 (TREK-1) is a polymodal two-pore domain leak potassium channel that responds to external pH, GPCR-mediated phosphorylation signals, and temperature through the action of distinct sensors within the channel. How the various intracellular and extracellular sensory elements control channel function remains unresolved. Here, we show that the K(2P)2.1 (TREK-1) intracellular C-terminal tail (Ct), a major sensory element of the channel, perceives metabolic and thermal commands and relays them to the extracellular C-type gate through transmembrane helix M4 and pore helix 1. By decoupling Ct from the pore-forming core, we further demonstrate that Ct is the primary heat-sensing element of the channel, whereas, in contrast, the pore domain lacks robust temperature sensitivity. Together, our findings outline a mechanism for signal transduction within K(2P)2.1 (TREK-1) in which there is a clear crosstalk between the C-type gate and intracellular Ct domain. In addition, our findings support the general notion of the existence of modular temperature-sensing domains in temperature-sensitive ion channels. This marked distinction between gating and sensory elements suggests a general design principle that may underlie the function of a variety of temperature-sensitive channels.
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spelling pubmed-34110762012-08-03 Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains Bagriantsev, Sviatoslav N Clark, Kimberly A Minor, Daniel L EMBO J Article K(2P)2.1 (TREK-1) is a polymodal two-pore domain leak potassium channel that responds to external pH, GPCR-mediated phosphorylation signals, and temperature through the action of distinct sensors within the channel. How the various intracellular and extracellular sensory elements control channel function remains unresolved. Here, we show that the K(2P)2.1 (TREK-1) intracellular C-terminal tail (Ct), a major sensory element of the channel, perceives metabolic and thermal commands and relays them to the extracellular C-type gate through transmembrane helix M4 and pore helix 1. By decoupling Ct from the pore-forming core, we further demonstrate that Ct is the primary heat-sensing element of the channel, whereas, in contrast, the pore domain lacks robust temperature sensitivity. Together, our findings outline a mechanism for signal transduction within K(2P)2.1 (TREK-1) in which there is a clear crosstalk between the C-type gate and intracellular Ct domain. In addition, our findings support the general notion of the existence of modular temperature-sensing domains in temperature-sensitive ion channels. This marked distinction between gating and sensory elements suggests a general design principle that may underlie the function of a variety of temperature-sensitive channels. European Molecular Biology Organization 2012-08-01 2012-06-22 /pmc/articles/PMC3411076/ /pubmed/22728824 http://dx.doi.org/10.1038/emboj.2012.171 Text en Copyright © 2012, European Molecular Biology Organization https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.
spellingShingle Article
Bagriantsev, Sviatoslav N
Clark, Kimberly A
Minor, Daniel L
Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains
title Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains
title_full Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains
title_fullStr Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains
title_full_unstemmed Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains
title_short Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains
title_sort metabolic and thermal stimuli control k(2p)2.1 (trek-1) through modular sensory and gating domains
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411076/
https://www.ncbi.nlm.nih.gov/pubmed/22728824
http://dx.doi.org/10.1038/emboj.2012.171
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