A phospholipid sensor controls mechanogating of the K+ channel TREK-1

AUTOR(ES)

Chemin, Jean

FONTE

Nature Publishing Group

RESUMO

TREK-1 (KCNK2 or K2P2.1) is a mechanosensitive K2P channel that is opened by membrane stretch as well as cell swelling. Here, we demonstrate that membrane phospholipids, including PIP2, 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-, pHi- and voltage-dependent gating.

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