内体
细胞生物学
生物化学
细胞器
生物
化学
生物物理学
受体
作者
Gihan S. Gunaratne,Eugen Brǎiloiu,Sushil Kumar,Yu Yuan,James T. Slama,Timothy F. Walseth,Sandip Patel,Jonathan S. Marchant
出处
期刊:Science Signaling
[American Association for the Advancement of Science (AAAS)]
日期:2023-08-22
卷期号:16 (799)
被引量:1
标识
DOI:10.1126/scisignal.adg0485
摘要
The second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) evokes calcium ion (Ca 2+ ) 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-Ca 2+ 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 Ca 2+ 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 Ca 2+ release and function through TPCs.
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