Gunaratne, GS; Brailoiu, E; He, S; Unterwald, EM; Patel, S; Slama, JT; Walseth, TF; Gunaratne, GS; Brailoiu, E; He, S; Unterwald, EM; Patel, S; Slama, JT; Walseth, TF; Marchant, JS; - view fewer (2021) Essential requirement for JPT2 in NAADP-evoked Ca²⁺ signaling. Science Signaling , 14 (675) , Article eabd5605. 10.1126/scisignal.abd5605.

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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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