Faculty Collaboration Database

Convergent activation of two-pore channels mediated by the NAADP-binding proteins JPT2 and LSM12. Sci Signal 2023 Aug 22;16(799):eadg0485

Date

08/22/2023

Pubmed ID

37607218

Pubmed Central ID

PMC10639087

DOI

10.1126/scisignal.adg0485

Scopus ID

2-s2.0-85168792524 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

The second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) evokes calcium ion (Ca²⁺) release from endosomes and lysosomes by activating two-pore channels (TPCs) on these organelles. Rather than directly binding to TPCs, NAADP associates with proteins that indirectly confer NAADP sensitivity to the TPC complex. We investigated whether and how the NAADP-binding proteins Jupiter microtubule-associated homolog 2 (JPT2) and like-Sm protein 12 (LSM12) contributed to NAADP-TPC-Ca²⁺ signaling in human cells. Biochemical and functional analyses revealed that recombinant JPT2 and LSM12 both bound to NAADP with high affinity and that endogenous JPT2 and LSM12 independently associated with TPC1 and TPC2. On the basis of knockout and rescue analyses, both NAADP-binding proteins were required to support NAADP-evoked Ca²⁺ signaling and contributed to endolysosomal trafficking of pseudotyped coronavirus particles. These data reveal that the NAADP-binding proteins JPT2 and LSM12 convergently regulate NAADP-evoked Ca²⁺ release and function through TPCs.

Author List

Gunaratne GS, Brailoiu E, Kumar S, Yuan Y, Slama JT, Walseth TF, Patel S, 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

Carrier Proteins
Coronavirus Infections
Endosomes
Humans
NADP