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Essential requirement for JPT2 in NAADP-evoked Ca2+ signaling

Gunaratne, Gihan S.
; 
Brailoiu, Eugen
; 
He, Shijun
; ; 
Patel, Sandip
; ; 
Walseth, Timothy F.
; 
Marchant, Jonathan S.
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Post-print
Date
2021-03-23
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Committee member
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Center for Substance Abuse Research (Temple University)
Department
Neural Sciences
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http://hdl.handle.net/20.500.12613/7032
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COVID-19 Research
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Brailoiu-EtAl-JournalArticle-2021-03.pdf
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DOI
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.
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American Association for the Advancement of Science
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Science Signaling, Vol. 14
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