Convergent activation of two-pore channels mediated by the NAADP-binding proteins JPT2 and LSM12. Sci Signal 2023 Aug 22;16(799):eadg0485
Date
08/22/2023Pubmed ID
37607218Pubmed Central ID
PMC10639087DOI
10.1126/scisignal.adg0485Scopus ID
2-s2.0-85168792524 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
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 JSAuthor
Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Carrier ProteinsCoronavirus Infections
Endosomes
Humans
NADP
RNA Splicing Factors