An NAADP-gated two-pore channel targeted to the plasma membrane uncouples triggering from amplifying Ca2+ signals.
An NAADP-gated two-pore channel targeted to the plasma membrane uncouples triggering from amplifying Ca2+ signals.
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DOI：
10.1074/jbc.m110.162073
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发表时间：
2010-12-03
期刊：
影响因子：
--
通讯作者：
Patel S
中科院分区：
文献类型：
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作者：
Brailoiu E;Rahman T;Churamani D;Prole DL;Brailoiu GC;Hooper R;Taylor CW;Patel S
烟酸腺嘌呤二核苷酸磷酸（NAADP）是一种普遍存在的信使，被认为可以通过双孔通道（TPC）刺激酸性细胞器中的Ca 2+释放。很难从其通过内质网Ca2+储存的扩增中解决该触发事件，从而引发了原型细胞内Ca2+通道是NAADP的主要靶点的推测。在这里，我们重新定向TPC 2从溶酶体到质膜，并表明NAADP引起钙离子流入的ryanodine受体的独立性，它激活的钙离子渗透通道，其电导率降低了一个假定的孔内的残基突变。因此，我们解偶联TPC 2从放大途径，并证明它是一个成孔亚基的NAADP门控的钙离子通道。
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a ubiquitous messenger proposed to stimulate Ca2+ release from acidic organelles via two-pore channels (TPCs). It has been difficult to resolve this trigger event from its amplification via endoplasmic reticulum Ca2+ stores, fuelling speculation that archetypal intracellular Ca2+ channels are the primary targets of NAADP. Here, we redirect TPC2 from lysosomes to the plasma membrane and show that NAADP evokes Ca2+ influx independent of ryanodine receptors and that it activates a Ca2+-permeable channel whose conductance is reduced by mutation of a residue within a putative pore. We therefore uncouple TPC2 from amplification pathways and prove that it is a pore-forming subunit of an NAADP-gated Ca2+ channel.