Essential requirement for JPT2 in NAADP-evoked Ca(2+) signaling.

Essential requirement for JPT2 in NAADP-evoked Ca(2+) signaling.
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NAADP引起的CA(2+)信号传导中JPT2的基本要求。

DOI:
10.1126/scisignal.abd5605
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发表时间:
2021-03-23
期刊:
影响因子:
7.3
通讯作者:
Marchant JS
Marchant JS
中科院分区:
生物学1区
文献类型:
--
作者:
Gunaratne GS;Brailoiu E;He S;Unterwald EM;Patel S;Slama JT;Walseth TF;Marchant JS

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烟酸腺嘌呤二核苷酸磷酸(NAADP)是第二信使,通过激活两个孔通道(TPC)从酸性细胞器释放钙离子,调节内溶酶体转运事件。NAADP的作用是由身份未知的NAADP结合蛋白(S)介导的,该蛋白赋予NAADP对TPC的敏感性。在这里,我们使用了一个基于NAADP的光探针来分离人NAADP结合蛋白,并确定Jupiter微管相关同源蛋白2(JPT2)是一种TPC辅助蛋白,是内源性NAADP诱导的钙信号转导所必需的。严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)假病毒通过内溶酶系统转运也需要JPT2。因此,JPT2是NAADP受体复合体的一个组成部分,对于TPC依赖的钙信号和冠状病毒进入的控制是必不可少的。
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that releases Ca2+ 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 Ca2+ 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 Ca2+ signaling and control of coronaviral entry.
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