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

Sci Signal. 2021 Mar 23;14(675):eabd5605. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Affinity Labels
  • Animals
  • COVID-19 / metabolism*
  • COVID-19 / virology*
  • Calcium Channels / metabolism
  • Calcium Signaling / physiology*
  • Carrier Proteins / metabolism
  • Click Chemistry / methods
  • 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

Substances

  • Affinity Labels
  • Calcium Channels
  • Carrier Proteins
  • JPT2 protein, human
  • Microtubule-Associated Proteins
  • Recombinant Proteins
  • TPCN1 protein, human
  • NADP
  • NAADP