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

• Published in: Science signaling Vol. 14; no. 675
• Main Authors: Gunaratne, Gihan S, Brailoiu, Eugen, He, Shijun, Unterwald, Ellen M, Patel, Sandip, Slama, James T, Walseth, Timothy F, Marchant, Jonathan S
• Format: Journal Article
• Language: English
• Published: United States 23.03.2021
• Subjects: Affinity Labels; Animals; Calcium Channels - metabolism; Calcium Signaling - physiology; Carrier Proteins - metabolism; Click Chemistry - methods; COVID-19 - metabolism; COVID-19 - virology; Gene Knockdown Techniques; HEK293 Cells; Humans; Microtubule-Associated Proteins - antagonists & inhibitors; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; NADP - analogs & derivatives; NADP - metabolism; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; SARS-CoV-2 - physiology; Second Messenger Systems - physiology; Transcriptome; Virus Internalization
• ISSN: 1937-9145
• 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.