Convergent activation of two-pore channels mediated by the NAADP-binding proteins JPT2 and LSM12.
Convergent activation of two-pore channels mediated by the NAADP-binding proteins JPT2 and LSM12.
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DOI：
10.1126/scisignal.adg0485
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发表时间：
2023-08-22
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
第二信使烟酸腺嘌呤二核苷酸磷酸(NAADP)通过激活细胞器上的双孔通道(TPC)，引起内体和溶酶体释放钙离子(Ca~(2+))。NAADP不是直接与TPC结合，而是与间接赋予NAADP对TPC复合体敏感性的蛋白质结合。我们研究了NAADP结合蛋白Jupiter微管相关同源蛋白2(JPT2)和LSM12(LSM12)是否以及如何在人细胞中对NAADP-TPC-Ca~(2+)信号起作用。生化和功能分析表明，重组JPT2和LSM12均与NAADP高亲和力结合，内源性JPT2和LSM12与TPC1和TPC2独立结合。根据基因敲除和挽救分析，这两个NAADP结合蛋白都需要支持NAADP诱导的钙信号，并有助于假型冠状病毒颗粒的内溶酶体转运。这些数据表明，NAADP结合蛋白JPT2和LSM12通过TPC共同调节NAADP诱导的钙释放和功能。
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.
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影响因子：
13.8
作者：
Marchant JS;Gunaratne GS;Cai X;Slama JT;Patel S
通讯作者：
Patel S
NAADP引起的CA（2+）信号传导中JPT2的基本要求。
影响因子：
7.3
作者：
Gunaratne GS;Brailoiu E;He S;Unterwald EM;Patel S;Slama JT;Walseth TF;Marchant JS
通讯作者：
Marchant JS
影响因子：
4.8
作者：
Lin-Moshier, Yaping;Walseth, Timothy F.;Marchant, Jonathan S.
通讯作者：
Marchant, Jonathan S.
影响因子：
3.9
作者：
Morgan, Anthony J.;Davis, Lianne C.;Galione, Antony
通讯作者：
Galione, Antony
DOI：
10.1083/jcb.200904073
发表时间：
2009-07-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Brailoiu E;Churamani D;Cai X;Schrlau MG;Brailoiu GC;Gao X;Hooper R;Boulware MJ;Dun NJ;Marchant JS;Patel S
通讯作者：
Patel S