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A phospholipid sensor controls mechanogating of the K + channel TREK‐1
Author(s) -
Chemin Jean,
Patel Amanda Jane,
Duprat Fabrice,
Lauritzen Inger,
Lazdunski Michel,
Honoré Eric
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600494
Subject(s) - mechanosensitive channels , phospholipid , gating , biophysics , membrane , protonation , biology , cell membrane , conductance , ion channel , biochemistry , chemistry , ion , physics , receptor , organic chemistry , condensed matter physics
TREK‐1 (KCNK2 or K 2P 2.1) is a mechanosensitive K 2P channel that is opened by membrane stretch as well as cell swelling. Here, we demonstrate that membrane phospholipids, including PIP 2 , control channel gating and transform TREK‐1 into a leak K + conductance. A carboxy‐terminal positively charged cluster is the phospholipid‐sensing domain that interacts with the plasma membrane. This region also encompasses the proton sensor E306 that is required for activation of TREK‐1 by cytosolic acidosis. Protonation of E306 drastically tightens channel–phospholipid interaction and leads to TREK‐1 opening at atmospheric pressure. The TREK‐1–phospholipid interaction is critical for channel mechano‐, pH i ‐ and voltage‐dependent gating.