Structure Function of Mechanically Activated Ion Channel

描述（由申请人提供）：对于触觉/痛觉和听觉，直接响应机械力激活的阳离子通道已被表征。此外，包括血管平滑肌细胞在内的许多其他细胞类型也表达这种机械激活（MA）阳离子电流，并且机械转导与各种生物过程和疾病有关。然而，值得注意的是，这些离子通道在脊椎动物中的身份仍然未知。我们最近在脊椎动物中发现了名为Piezo1和Piezo2的MA阳离子通道成分。在多种哺乳动物细胞系中表达Piezos可诱导大的MA阳离子电流。压电在与机械传导相关的多种组织中表达。Piezo1和Piezo2包含超过24个假定的跨膜结构域，但不类似于已知的离子通道或其他蛋白质类别。关于这些蛋白质的结构还有许多重要的未解之谜。在这里，我们假设Piezo1寡聚形成机械激活离子通道的含孔亚基。

DESCRIPTION (provided by applicant): For sense of touch/pain and hearing, cation channels that are directly activated in response to mechanical forces have been characterized. In addition, many other cell types including vascular smooth muscle cells express such mechanically-activated (MA) cationic currents, and mechanotransduction is implicated in various biological processes and diseases. Remarkably, however, the identity of these ion channels in vertebrates has remained unknown. We recently identified MA cation channel components in vertebrates named Piezo1 and Piezo2. Expressing Piezos in a variety of mammalian cell lines induce large MA cationic currents. Piezos are expressed in a variety of tissues implicated in mechanotransduction. Piezo1 and Piezo2 contain over 24 putative transmembrane domains but do not resemble known ion channels or other protein classes. Many important open questions remain about the structure of these proteins. Here, we hypothesize that Piezo1 oligomerizes to form pore-containing subunits of mechanically-activated ion channels.