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


ABSTRACT: 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

SUBMITTER: Bagriantsev SN 

PROVIDER: S-EPMC3411076 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature