期刊
SCIENCE SIGNALING
卷 14, 期 675, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.abd5605
关键词
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资金
- NIH [GM088790, R15-GM131329, P30 DA 013429]
- NSF [2027748]
- BBSRC [BB/N01524X/1, BB/T015853/1]
- BBSRC [BB/T015853/1] Funding Source: UKRI
- Division Of Integrative Organismal Systems
- Direct For Biological Sciences [2027748] Funding Source: National Science Foundation
The study identified JPT2 as an essential component of the NAADP receptor complex, required for TPC-dependent Ca2+ signaling and control of coronaviral entry through the endolysosomal system.
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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