Walther-Straub-Institute of Pharmacology and Toxicology, Faculty of Medicine, LMU Munich, Munich, Germany.
Purinergic Signal. 2022 Dec;18(4):495-498. doi: 10.1007/s11302-022-09893-z. Epub 2022 Aug 12.
High concentration of extracellular ATP acts as a danger signal that is sensed by the P2X7 receptor (P2X7R). This ATP-gated ion channel has been shown to induce multiple metabotropic events such as changes in plasma membrane composition and morphology, ectodomain shedding, activation of lipases, kinases, and transcription factors as well as cytokine release. The specific signaling pathways and molecular mechanisms remain largely obscure. Using an unbiased genome-scale CRISPR/Cas9 screening approach in a murine T cell line, Ryoden et al. (2022, 2020) identified three proteins involved in P2X7 regulation and signaling: Essential for Reactive Oxygen Species (EROS) is essential for P2X7 folding and maturation, and Xk and Vsp13a are required for P2X7-mediated phosphatidyl serine exposure and cell lysis. They further provide evidence for an interaction of Xk and Vsp13a at the plasma membrane and confirm the role of Xk in ATP-induced cytolysis in primary CD25CD4 T cells from Xk mice.
高浓度的细胞外 ATP 作为一种危险信号，被 P2X7 受体 (P2X7R) 感知。这种 ATP 门控离子通道已被证明能诱导多种代谢型事件，如质膜组成和形态的变化、细胞外结构域脱落、脂酶、激酶和转录因子的激活以及细胞因子的释放。特定的信号通路和分子机制在很大程度上仍不清楚。Ryoden 等人在 2022 年和 2020 年使用一种无偏基因组规模的 CRISPR/Cas9 筛选方法在鼠 T 细胞系中发现了三种参与 P2X7 调节和信号转导的蛋白质：活性氧必需蛋白（EROS）对于 P2X7 的折叠和成熟是必需的，而 Xk 和 Vsp13a 对于 P2X7 介导的磷脂酰丝氨酸暴露和细胞裂解是必需的。他们进一步提供了 Xk 和 Vsp13a 在质膜上相互作用的证据，并证实了 Xk 在 Xk 小鼠的原代 CD25CD4 T 细胞中 ATP 诱导的细胞溶解中的作用。
