Department of Pharmacology, University of Minnesota Medical School, 312 Church Street, Minneapolis, MN 55455, USA.
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Sci Signal. 2021 Mar 23;14(675):eabd5605. doi: 10.1126/scisignal.abd5605.
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that releases Ca from acidic organelles through the activation of two-pore channels (TPCs) to regulate endolysosomal trafficking events. NAADP action is mediated by NAADP-binding protein(s) of unknown identity that confer NAADP sensitivity to TPCs. Here, we used a "clickable" NAADP-based photoprobe to isolate human NAADP-binding proteins and identified Jupiter microtubule-associated homolog 2 (JPT2) as a TPC accessory protein required for endogenous NAADP-evoked Ca signaling. JPT2 was also required for the translocation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus through the endolysosomal system. Thus, JPT2 is a component of the NAADP receptor complex that is essential for TPC-dependent Ca signaling and control of coronaviral entry.
烟酰胺腺嘌呤二核苷酸磷酸（NAADP）是一种第二信使，通过激活双孔通道（TPCs）从酸性细胞器中释放 Ca2+，从而调节内体溶酶体运输事件。NAADP 的作用是由未知身份的 NAADP 结合蛋白介导的，这些蛋白使 TPCs 对 NAADP 敏感。在这里，我们使用一种“可点击”的基于 NAADP 的光探针来分离人类 NAADP 结合蛋白，并鉴定出木星微管相关同源物 2（JPT2）作为一种 TPC 辅助蛋白，它是内源性 NAADP 诱导的 Ca2+信号所必需的。JPT2 也需要严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）假病毒通过内体溶酶体系统的易位。因此，JPT2 是 NAADP 受体复合物的一个组成部分，对于 TPC 依赖性 Ca2+信号和控制冠状病毒进入是必不可少的。
