Faculty Collaboration Database

Essential requirement for JPT2 in NAADP-evoked Ca²⁺ signaling. Sci Signal 2021 Mar 23;14(675)

Date

03/25/2021

Pubmed ID

33758061

Pubmed Central ID

PMC8315109

DOI

10.1126/scisignal.abd5605

Scopus ID

2-s2.0-85103059022 (requires institutional sign-in at Scopus site)   87 Citations

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.

Author List

Gunaratne GS, Brailoiu E, He S, Unterwald EM, Patel S, Slama JT, Walseth TF, Marchant JS

Author

Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Affinity Labels
Animals
Calcium Channels
Calcium Signaling
Carrier Proteins
Click Chemistry
Gene Knockdown Techniques
HEK293 Cells
Humans
Microtubule-Associated Proteins
NADP
Recombinant Proteins
Second Messenger Systems
Transcriptome
Virus Internalization