TMEM163 调节 ATP 门控 P2X 受体和行为。
TMEM163 Regulates ATP-Gated P2X Receptor and Behavior.
机构信息
Department of Cellular and Molecular Physiology, Department of Neuroscience, Program in Cellular Neuroscience, Neurodegeneration and Repair, The Yale Kavli Institute, Yale University School of Medicine, New Haven, CT 06520, USA; Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Cellular and Molecular Physiology, Department of Neuroscience, Program in Cellular Neuroscience, Neurodegeneration and Repair, The Yale Kavli Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
出版信息
Cell Rep. 2020 Jun 2;31(9):107704. doi: 10.1016/j.celrep.2020.107704.
Fast purinergic signaling is mediated by ATP and ATP-gated ionotropic P2X receptors (P2XRs), and it is implicated in pain-related behaviors. The properties exhibited by P2XRs vary between those expressed in heterologous cells and in vivo. Several modulators of ligand-gated ion channels have recently been identified, suggesting that there are P2XR functional modulators in vivo. Here, we establish a genome-wide open reading frame (ORF) collection and perform functional screening to identify modulators of P2XR activity. We identify TMEM163, which specifically modulates the channel properties and pharmacology of P2XRs. We also find that TMEM163 is required for full function of the neuronal P2XR and a pain-related ATP-evoked behavior. These results establish TMEM163 as a critical modulator of P2XRs in vivo and a potential target for the discovery of drugs for treating pain.
快速嘌呤能信号转导是由 ATP 和 ATP 门控离子型 P2X 受体（P2XR）介导的，它与疼痛相关行为有关。P2XR 在异源细胞和体内表现出的特性不同。最近已经鉴定出几种配体门控离子通道的调节剂，这表明体内存在 P2XR 功能调节剂。在这里，我们建立了一个全基因组开放阅读框（ORF）集合，并进行了功能筛选，以鉴定 P2XR 活性的调节剂。我们鉴定出 TMEM163，它特异性调节 P2XR 通道的特性和药理学。我们还发现 TMEM163 是神经元 P2XR 和与疼痛相关的 ATP 诱发行为的充分功能所必需的。这些结果确立了 TMEM163 作为体内 P2XR 的关键调节剂，以及发现治疗疼痛药物的潜在靶点。
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