Chemical and Genetic Engineering of Selective Ion Channel-Ligand Interactions
Chemical and Genetic Engineering of Selective Ion Channel-Ligand Interactions
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DOI：
10.1126/science.1206606
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发表时间：
2011-09-02
期刊：
影响因子：
56.9
通讯作者：
Sternson, Scott M.
中科院分区：
文献类型：
--
作者：
Magnus, Christopher J.;Lee, Peter H.;Sternson, Scott M.
离子通量介导特定细胞群中的基本生理和行为功能。需要不同离子电导的细胞类型特异性激活剂来探测这些效应。我们将化学和蛋白质工程相结合，系统地创建了具有正交药理学选择性和不同功能特性的配体门控离子通道（LGIC）工具箱。 LGIC 及其小分子效应器能够激活遗传特定细胞类型中的一系列离子电导。为神经元扰动而构建的 LGIC 可用于选择性地操纵体内哺乳动物大脑中的神经元活动。通过这种方法获得的离子通道工具的多样性将有助于检查神经元活动和动物行为之间的关系，以及需要化学控制离子电导的细胞生物学和生理学应用。
Ionic flux mediates essential physiological and behavioral functions in defined cell populations. Cell type-specific activators of diverse ionic conductances are needed for probing these effects. We combined chemistry and protein engineering to enable the systematic creation of a toolbox of ligand-gated ion channels (LGICs) with orthogonal pharmacologic selectivity and divergent functional properties. The LGICs and their small-molecule effectors were able to activate a range of ionic conductances in genetically specified cell types. LGICs constructed for neuronal perturbation could be used to selectively manipulate neuron activity in mammalian brains in vivo. The diversity of ion channel tools accessible from this approach will be useful for examining the relationship between neuronal activity and animal behavior, as well as for cell biological and physiological applications requiring chemical control of ion conductance.