Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K+ channels
Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K+ channels
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DOI：
10.1073/pnas.1320768111
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发表时间：
2014-03-04
影响因子：
11.1
通讯作者：
MacKinnon, Roderick
中科院分区：
文献类型：
--
作者：
Brohawn, Stephen G.;Su, Zhenwei;MacKinnon, Roderick
机械敏感性离子通道是神经元对触觉、听觉和其他机械刺激的感觉中的物理力的反应的基础。真核生物机械敏感离子通道中力传递的基本原理尚不清楚。机械力是像原核生物中的机械传感器那样直接从膜传递到通道，还是通过连接在通道上的大分子链介导？在这里，我们表明，在细胞中，K+通道TRAAK（K2P4.1）是响应机械力类似的离子通道Piezo1和TRAAK的机械激活可以电对抗Piezo1激活。然后，我们表明，在TRAAK和TREK1（K2P2.1）双孔域K+（K2P）通道的力转导的生物物理起源来自脂质膜，而不是从连接的系绳。这些发现将原核机械敏感通道MscL和MscS建立的“来自脂质的力”原理扩展到这些真核机械敏感K+通道。
Mechanosensitive ion channels underlie neuronal responses to physical forces in the sensation of touch, hearing, and other mechanical stimuli. The fundamental basis of force transduction in eukaryotic mechanosensitive ion channels is unknown. Are mechanical forces transmitted directly from membrane to channel as in prokaryotic mechanosensors or are they mediated through macromolecular tethers attached to the channel? Here we show in cells that the K+ channel TRAAK (K2P4.1) is responsive to mechanical forces similar to the ion channel Piezo1 and that mechanical activation of TRAAK can electrically counter Piezo1 activation. We then show that the biophysical origins of force transduction in TRAAK and TREK1 (K2P2.1) two-pore domain K+ (K2P) channels come from the lipid membrane, not from attached tethers. These findings extend the "force-from-lipid" principle established for prokaryotic mechanosensitive channels MscL and MscS to these eukaryotic mechanosensitive K+ channels.