摘要
P2X3 受体在感觉处理和传播起一个重要作用。为它在主要感觉神经原的功能重要的 P2X3 receptorare 的集会和 trafficking。作为一个重要发炎调停人， ATP 在主要感觉神经原附近被免除 differentcell 类型，特别在病理学的疼痛条件下面。这里，我们显示出那，在表示 recombinant P2X3 受体的 HEK293T 房间并且在老鼠 primarysensory 神经原的 P2X3 受体的 -MeATP dramaticallypromoted 膜交货。， -MeATP 导致的 P2X3 调停受体的 Ca <sup>2+</sup> 流入，它推进激活的 Ca <sup>2+</sup>/calmodulin-dependent 蛋白质 kinase II (CaMKII ) 。P2X3 受体的 N 终点为 CaMKII 绑定负责，而在 C 终点的 Thr <sup>388</sup> 是由 CaMKII 的 phosphorylated。Thr <sup>388</sup> phosphorylation 增加了 P2X3 受体绑定到 caveolin-1。Caveolin-1 击倒废除， P2X3 受体的 -MeATP-induced membraneinsertion。而且，， -MeATP 驾驶了 P2X2 receptorwith 的调停 CaMKII 的膜 coinsertion P2X3 受体。由于 Thr <sup>388</sup> phosphorylation 的房间膜上的增加的 P2X3 受体便于 P2X3 调停受体的信号 transduction。一起，我们的数据显示那 CaMKII 和 caveolin-1cooperate 驾驶 P2X3 受体的导致 ligand 的膜交货并且可以提供 P2X3 受体 sensitizationin 疼痛开发的机制。
The P2X3 receptor plays a vital role in sensory processing and transmission. The assembly and trafficking of the P2X3 receptor are important for its function in primary sensory neurons. As an important inflammation mediator, ATP is released from different cell types around primary sensory neurons, especially under pathological pain conditions. Here, we showthat α, β-MeATP dramatically promoted membrane delivery of the P2X3 receptor both in HEK293T celts expressing recombinant P2X3 receptor and in rat primary sensory neurons. α, β-MeATP induced P2X3 receptor-mediated Ca^2＋ influx, which further activated Ca^2＋/calmodulin-dependent protein kinase Ilec （CaMKIIα）. The N terminus of the P2X3 receptor was responsible for CaMKIleα binding, whereas Thr38s in the C terminus was phosphorylated by CaMKIIα. Thr^388 phosphorylation increased P2X3 receptor binding to caveoUn-1. CaveoUn-1 knockdown abrogated the α, β-MeATP-induced membrane insertion of the P2X3 receptor. Moreover,α, β-MeATP drove the CaMKIlec-mediated membrane coinsertion of the P2X2 receptor with the P2X3 receptor. The increased P2X3 receptors on the cell membrane that are due to Thr388 phosphorytation facilitated P2X3 receptor-mediated signal transduction. Together, our data indicate that CaMKIIoL and caveoUn-1 cooperate to drive Ugand-induced membrane delivery of the P2X3 receptor and may provide a mechanism of P2X3 receptor sensitization in pain development.
