title: A phospholipid sensor controls mechanogating of the K+ channel TREK-1.
abstract: 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.
authors.affiliation: Institut de Pharmacologie, Moléculaire et Cellulaire, Institut Paul Hamel, Sophia Antipolis, Valbonne, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Chemin
authors.forename: Amanda Jane
authors.initials: AJ
authors.lastname: Patel
authors.forename: Fabrice
authors.initials: F
authors.lastname: Duprat
authors.forename: Inger
authors.initials: I
authors.lastname: Lauritzen
authors.forename: Michel
authors.initials: M
authors.lastname: Lazdunski
authors.forename: Eric
authors.initials: E
authors.lastname: Honoré
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015374:Biosensing Techniques; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011522:Protons; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D019269:Phosphatidylinositol 4,5-Diphosphate; D026902:Potassium Channel Blockers; D024683:Potassium Channels, Tandem Pore Domain; D011522:Protons; D011993:Recombinant Fusion Proteins; C103742:potassium channel protein TREK-1; D011188:Potassium