TMEM150C/Tentonin3 Is a Regulator of Mechano-gated Ion Channels.

TMEM150C/Tentonin3 Is a Regulator of Mechano-gated Ion Channels.
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DOI:
10.1016/j.celrep.2018.03.094
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发表时间:
2018-04-17
期刊:
影响因子:
8.8
通讯作者:
Bagriantsev SN
Bagriantsev SN
中科院分区:
生物学1区
文献类型:
--
作者:
Anderson EO;Schneider ER;Matson JD;Gracheva EO;Bagriantsev SN

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神经元的机械敏感性依赖于机械化的离子通道,但调节其活动的途径仍然知之甚少。TMEM150C被认为介导本体感觉神经元的机械激活电流。在这里,我们用两种独立的机械刺激方法研究了TMEM150C与不同类别的机械门控离子通道(Piezo2、Piezo1和钾通道Trek-1)的功能相互作用。我们发现,TMEM150C显著延长了三种通道产生的机械电流的持续时间,降低了Piezo2的表观激活阈值,并在Piezo1中诱导了持续电流。我们还发现,TMEM150C与Piezo2在三叉神经细胞中共表达,将其作用扩展到本体感受器之外。最后,我们从触觉觅食家鸭的三叉神经细胞中克隆了TMEM150C,并表明它的功能与小鼠同源基因相似,证明了脊椎动物之间的进化保守。我们的研究表明,TMEM150C是不同类别的机械门控离子通道的通用调节器。机械门控离子通道是躯体感觉、本体感觉、听力、血管扩张和轴突生长所必需的。Anderson et al.结果表明,跨膜蛋白TMEM150C促进不同类别的机械门控离子通道的活性:PIEZO1/2和钾选择通道Trek-1。这项研究揭示了TMEM150C作为一种进化保守的机械敏感性调节因子的作用。
Neuronal mechano-sensitivity relies on mechanogated ion channels, but pathways regulating their activity remain poorly understood. TMEM150C was proposed to mediate mechano-activated current in proprioceptive neurons. Here, we studied functional interaction of TMEM150C with mechano-gated ion channels from different classes (Piezo2, Piezo1, and the potassium channel TREK-1) using two independent methods of mechanical stimulation. We found that TMEM150C significantly prolongs the duration of the mechano-current produced by all three channels, decreases apparent activation threshold in Piezo2, and induces persistent current in Piezo1. We also show that TMEM150C is co-expressed with Piezo2 in trigeminal neurons, expanding its role beyond proprioceptors. Finally, we cloned TMEM150C from the trigeminal neurons of the tactile-foraging domestic duck and showed that it functions similarly to the mouse ortholog, demonstrating evolutionary conservation among vertebrates. Our studies reveal TMEM150C as a general regulator of mechano-gated ion channels from different classes. Mechano-gated ion channels are essential for somatosensation, proprioception, hearing, vasodilation, and axonal growth. Anderson et al. show that the transmembrane protein TMEM150C facilitates activity of mechano-gated ion channels from different classes: Piezo1/2 and the potassium-selective channel TREK-1. This study reveals a role for TMEM150C as an evolutionarily conserved regulator of mechano-sensitivity.
k(2p)2.1(Trek-1) - 激活器复合物揭示了一个隐秘的选择性滤波器结合位点。
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