2. Academic Validation
  3. Essential requirement for JPT2 in NAADP-evoked Ca2+ signaling

Essential requirement for JPT2 in NAADP-evoked Ca2+ signaling

  • Sci Signal. 2021 Mar 23;14(675):eabd5605. doi: 10.1126/scisignal.abd5605.
Gihan S Gunaratne 1 2,  Eugen Brailoiu 3,  Shijun He 4,  Ellen M Unterwald 3,  Sandip Patel 5,  James T Slama 3,  Timothy F Walseth 1,  Jonathan S Marchant 6
Affiliations

Affiliations

  • 1 Department of Pharmacology, University of Minnesota Medical School, 312 Church Street, Minneapolis, MN 55455, USA.
  • 2 Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
  • 3 Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
  • 4 Department of Medicinal and Biological Chemistry, University of Toledo College of Pharmacy and Pharmaceutical Sciences, 3000 Arlington Avenue, Toledo, OH 43614, USA.
  • 5 Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
  • 6 Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. jmarchant@mcw.edu.
PMID: 33758061 DOI: 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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