Piezo1: properties of a cation selective mechanical channel.

Piezo1: properties of a cation selective mechanical channel.
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DOI:
10.4161/chan.21050
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发表时间:
2012-07
期刊:
Channels (Austin, Tex.)
影响因子:
--
通讯作者:
Sachs F
Sachs F
中科院分区:
其他
文献类型:
--
作者:
Gottlieb PA;Sachs F

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已发现,压电离子通道对细胞的机械反应是必不可少的。这些通道首先被证明存在于Neuro2A细胞中,并通过减弱机械反应的siRNAs确定了该基因。压电通道大约有2500个氨基酸长,有24-32个跨膜区,似乎可以组装成四聚体,不需要其他蛋白质就能发挥作用。它们的反转电位约为0 mV,表现出电压依赖性的失活。该通道在脂质体中具有结构性活性,表明不需要细胞骨架元素。异源表达的Piezo蛋白可以在原本不敏感的细胞中产生机械敏感性。细胞外MSC抑制肽GsMTx4可阻断PIEZO1电流。GsMTx4的两种对映体形式都以类似于内源性机械通道的方式抑制通道活动。PIEZO1可以采用补药(非失活)形式,反复刺激。向非失活形式的转变通常发生在大的通道组中,这表明通道存在于域中,一旦域被攻破,成员同时采用新的属性。Piezo蛋白与细胞中的生理反应有关,例如对果蝇幼虫有害刺激的反应。最近测量细胞拥挤的工作表明,Piezo1对于去除多余的细胞而不发生细胞凋亡是必不可少的。PIEZO1突变也与一种名为干细胞症的遗传病中红细胞的病理反应有关。这些发现表明,Piezo1在细胞对机械刺激的反应中起着关键作用。
Piezo ion channels have been found to be essential for mechanical responses in cells. These channels were first shown to exist in Neuro2A cells, and the gene was identified by siRNAs that diminished the mechanical response. Piezo channels are approximately 2500 amino acids long, have between 24–32 transmembrane regions, and appear to assemble into tetramers and require no other proteins for activity. They have a reversal potential around 0 mV and show voltage dependent inactivation. The channel is constitutively active in liposomes, indicating that no cytoskeletal elements are required. Heterologous expression of the Piezo protein can create mechanical sensitivity in otherwise insensitive cells. Piezo1 currents in outside-out patches were blocked by the extracellular MSC inhibitor peptide GsMTx4. Both enantiomeric forms of GsMTx4 inhibited channel activity in a manner similar to endogenous mechanical channels. Piezo1 can adopt a tonic (non-inactivating) form with repeated stimulation. The transition to the non-inactivating form generally occurs in large groups of channels, indicating that the channels exist in domains, and once the domain is compromised, the members simultaneously adopt new properties. Piezo proteins are associated with physiological responses in cells, such as the reaction to noxious stimulus of Drosophila larvae. Recent work measuring cell crowding, shows that Piezo1 is essential for the removal of extra cells without apoptosis. Piezo1 mutations have also been linked to the pathological response of red blood cells in a genetic disease called Xerocytosis. These finding suggest that Piezo1 is a key player in cells’ responses to mechanical stimuli.
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