Essential requirement for JPT2 in NAADP-evoked Ca 2+ signaling
- 23 March 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Signaling
- Vol. 14 (675)
- https://doi.org/10.1126/scisignal.abd5605
Abstract
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.Keywords
Funding Information
- National Institutes of Health (GM088790)
- National Institutes of Health (GM131329)
- National Institutes of Health (P30 DA 013429)
- Biotechnology and Biological Sciences Research Council (BB/N01524X/1, BB/T015853/1)
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