Cardiovascular Research Institute, University of California, San Francisco, CA, 94158, USA.
Departments of Biochemistry and Biophysics, and Cellular and Molecular Pharmacology, University of California, San Francisco, CA, 94158, USA.
Pflugers Arch. 2018 May;470(5):733-744. doi: 10.1007/s00424-017-2102-z. Epub 2018 Jan 17.
Ion channels turn diverse types of inputs, ranging from neurotransmitters to physical forces, into electrical signals. Channel responses to ligands generally rely on binding to discrete sensor domains that are coupled to the portion of the channel responsible for ion permeation. By contrast, sensing physical cues such as voltage, pressure, and temperature arises from more varied mechanisms. Voltage is commonly sensed by a local, domain-based strategy, whereas the predominant paradigm for pressure sensing employs a global response in channel structure to membrane tension changes. Temperature sensing has been the most challenging response to understand and whether discrete sensor domains exist for pressure and temperature has been the subject of much investigation and debate. Recent exciting advances have uncovered discrete sensor modules for pressure and temperature in force-sensitive and thermal-sensitive ion channels, respectively. In particular, characterization of bacterial voltage-gated sodium channel (BacNa) thermal responses has identified a coiled-coil thermosensor that controls channel function through a temperature-dependent unfolding event. This coiled-coil thermosensor blueprint recurs in other temperature sensitive ion channels and thermosensitive proteins. Together with the identification of ion channel pressure sensing domains, these examples demonstrate that "local" domain-based solutions for sensing force and temperature exist and highlight the diversity of both global and local strategies that channels use to sense physical inputs. The modular nature of these newly discovered physical signal sensors provides opportunities to engineer novel pressure-sensitive and thermosensitive proteins and raises new questions about how such modular sensors may have evolved and empowered ion channel pores with new sensibilities.
离子通道将各种类型的输入（从神经递质到物理力）转化为电信号。通道对配体的响应通常依赖于与负责离子渗透的通道部分相连的离散传感器域的结合。相比之下，对电压、压力和温度等物理线索的感知则来自于更为多样化的机制。电压通常通过基于局部域的策略来感知，而压力感应的主要模式则采用通道结构对膜张力变化的整体响应。温度感应是最具挑战性的响应之一，是否存在离散的传感器域来感应压力和温度一直是许多研究和争论的主题。最近令人兴奋的进展分别揭示了压力敏感和温度敏感离子通道中用于压力和温度的离散传感器模块。特别是，对细菌电压门控钠离子通道（BacNa）热响应的特征分析确定了一个螺旋-卷曲热传感器，该传感器通过温度依赖的展开事件来控制通道功能。这种螺旋-卷曲热传感器蓝图在其他温度敏感离子通道和热敏蛋白中反复出现。与离子通道压力感应域的鉴定一起，这些例子表明存在用于感知力和温度的“局部”基于域的解决方案，并强调了通道用于感知物理输入的全局和局部策略的多样性。这些新发现的物理信号传感器的模块化性质为工程新型压力敏感和热敏蛋白提供了机会，并提出了关于这些模块化传感器如何进化以及如何赋予离子通道新的敏感性的新问题。
