Gunaratne, Gihan S; Brailoiu, Eugen; He, Shijun; Unterwald, Ellen M; Patel, Sandip; Slama, James T; Walseth, Timothy F; Marchant, Jonathan S
Essential requirement for JPT2 in NAADP-evoked Ca 2+ signaling
Teil von
  • Science signaling, 2021-03-23, Vol.14 (675)
Ort / Verlag
United States
Links zum Volltext
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.

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