Lsm12 is an NAADP receptor and a two-pore channel regulatory protein required for calcium mobilization from acidic organelles.
Lsm12 is an NAADP receptor and a two-pore channel regulatory protein required for calcium mobilization from acidic organelles.
复制标题
DOI：
10.1038/s41467-021-24735-z
复制
发表时间：
2021-08-06
影响因子：
16.6
通讯作者：
Yan J
中科院分区：
文献类型：
--
作者：
Zhang J;Guan X;Shah K;Yan J
烟酸腺嘌呤二核苷酸磷酸(NAADP)是一种强大的钙离子动员第二信使，能从酸性内溶酶体细胞器中唯一地动员钙离子。然而，NAADP受体的分子特性仍不清楚。鉴于NAADP信号中需要内溶酶体双孔通道(TPC1或TPC2)，我们对NAADP和TPC相互作用的蛋白质进行了亲和纯化和定量蛋白质组学分析。我们发现了一个与NAADP、TPC1和TPC2形成复合体的类Sm蛋白Lsm12。Lsm12通过其LSM结构域直接与NAADP结合，与TPC2共定位，并介导NAADP与分离的TPC2或含TPC2的膜的明显结合。Lsm12是必需的，并立即参与NAADP诱导的TPC活化和酸性贮藏中的钙动员。这些发现揭示了一个可能的RNA结合蛋白作为NAADP受体和TPC调节蛋白的功能，并为理解NAADP信号转导机制提供了分子基础。烟酸腺嘌呤二核苷酸磷酸(NAADP)是一种强大的钙离子动员第二信使，它能唯一地触发酸性内溶酶体细胞器中的钙离子释放。在这里，作者确认Lsm12是一种NAADP受体，通过与其LSM结构域上的NAADP结合，对NAADP诱导的溶酶体释放钙起关键作用。
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+-mobilizing second messenger which uniquely mobilizes Ca2+ from acidic endolysosomal organelles. However, the molecular identity of the NAADP receptor remains unknown. Given the necessity of the endolysosomal two-pore channel (TPC1 or TPC2) in NAADP signaling, we performed affinity purification and quantitative proteomic analysis of the interacting proteins of NAADP and TPCs. We identified a Sm-like protein Lsm12 complexed with NAADP, TPC1, and TPC2. Lsm12 directly binds to NAADP via its Lsm domain, colocalizes with TPC2, and mediates the apparent association of NAADP to isolated TPC2 or TPC2-containing membranes. Lsm12 is essential and immediately participates in NAADP-evoked TPC activation and Ca2+ mobilization from acidic stores. These findings reveal a putative RNA-binding protein to function as an NAADP receptor and a TPC regulatory protein and provides a molecular basis for understanding the mechanisms of NAADP signaling. Nicotinic acid adenine dinucleotide phosphate (NAADP) potent Ca2+ mobilizing second messenger which uniquely triggers Ca2+ release from acidic endolysosomal organelles. Here the authors identify Lsm12 as an NAADP receptor essential for NAADP-evoked Ca2+ release from lysosomes via NAADP binding on its Lsm domain.
登录
查看更多内容
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
DOI：
10.1074/jbc.m110.162073
发表时间：
2010-12-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Brailoiu E;Rahman T;Churamani D;Prole DL;Brailoiu GC;Hooper R;Taylor CW;Patel S
通讯作者：
Patel S
影响因子：
8
作者：
Boccaccio, Anna;Scholz-Starke, Joachim;Carpaneto, Armando
通讯作者：
Carpaneto, Armando
影响因子：
4.8
作者：
Lin-Moshier, Yaping;Walseth, Timothy F.;Marchant, Jonathan S.
通讯作者：
Marchant, Jonathan S.
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