ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology
ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology
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DOI：
10.1038/35079100
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发表时间：
2001-05-31
期刊：
影响因子：
64.8
通讯作者：
Scharenberg, AM
中科院分区：
文献类型：
--
作者：
Perraud, AL;Fleig, A;Scharenberg, AM
游离ADP-核糖（ADPR）是NAD水解的产物，也是钙释放第二信使环ADPR（cADPR）的分解产物，在脊椎动物系统中作为细胞内信号分子没有明确的作用。在这里，我们表明，一个350个氨基酸的蛋白质（命名为NUDT 9）和同源结构域（NUDT 9同源结构域）附近的羧基端的LTRPC 2/TrpC 7推定的阳离子通道（1）都作为特定的ADPR焦磷酸酶的功能。表达LTRPC 2的HEK-293细胞的全细胞和单通道分析表明，LTRPC 2作为钙渗透性阳离子通道发挥作用，其由游离ADPR特异性门控。天然LTRPC 2转录物的表达在许多组织中可检测到，包括U937单核细胞系，其中ADPR诱导与重组LTRPC 2介导的阳离子电流密切匹配的大阳离子电流（命名为I-ADPR）。这些结果表明，细胞内ADPR调节钙进入表达LTRPC 2的细胞。
Free ADP-ribose (ADPR), a product of NAD hydrolysis and a breakdown product of the calcium-release second messenger cyclic ADPR (cADPR), has no defined role as an intracellular signalling molecule in vertebrate systems. Here we show that a 350-amino-acid protein (designated NUDT9) and a homologous domain (NUDT9 homology domain) near the carboxy terminus of the LTRPC2/TrpC7 putative cation channel(1) both function as specific ADPR pyrophosphatases. Whole-cell and single-channel analysis of HEK-293 cells expressing LTRPC2 show that LTRPC2 functions as a calcium-permeable cation channel that is specifically gated by free ADPR. The expression of native LTRPC2 transcripts is detectable in many tissues including the U937 monocyte cell line, in which ADPR induces large cation currents (designated I-ADPR) that closely match those mediated by recombinant LTRPC2. These results indicate that intracellular ADPR regulates calcium entry into cells that express LTRPC2.