选择性离子通道-配体相互作用的化学和遗传工程。
Chemical and genetic engineering of selective ion channel-ligand interactions.
机构信息
Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
出版信息
Science. 2011 Sep 2;333(6047):1292-6. doi: 10.1126/science.1206606.
Abstract
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.
摘要
离子流介导特定细胞群体的基本生理和行为功能。需要具有不同离子传导能力的细胞类型特异性激活剂来探测这些影响。我们将化学和蛋白质工程相结合，以便能够系统地创建配体门控离子通道 (LGIC) 的工具包，这些通道具有正交药理学选择性和不同的功能特性。LGIC 及其小分子效应物能够激活遗传上指定的细胞类型中的一系列离子传导能力。用于神经元干扰的 LGIC 可用于选择性地在哺乳动物大脑中操纵神经元活动。从这种方法获得的离子通道工具的多样性将有助于研究神经元活动与动物行为之间的关系，以及需要化学控制离子传导的细胞生物学和生理学应用。
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