Calcium signaling via two-pore channels: local or global, that is the question.
Calcium signaling via two-pore channels: local or global, that is the question.
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DOI：
10.1152/ajpcell.00475.2009
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Evans AM
中科院分区：
文献类型：
--
作者：
Zhu MX;Ma J;Parrington J;Calcraft PJ;Galione A;Evans AM
最近，我们首次发现了双孔通道（TPCs，基因名称为TPCN）作为烟酸腺嘌呤二核苷酸磷酸（NAADP）门控的、内溶酶体靶向的钙释放通道的新家族。值得注意的是，tpc有三种亚型，TPC1-3，每种亚型都针对离散的酸性钙储存，即溶酶体（TPC2）和内体（TPC1和TPC3）。考虑到内源性NAADP受体的情况，NAADP结合与TPC2相关的高亲和力和低亲和力位点，从而诱导钙释放和同源脱敏，tpc作为NAADP门控钙释放通道是明确的。此外，naadp通过TPC2引起的钙信号通过TPC2的短发夹RNA敲除和bafilomycin消耗酸性钙储存而消融。然而，重要的是，naadp诱发的钙信号本质上是双相的，初始阶段是溶酶体通过TPC2释放钙，随后被内质网（ER）钙诱导钙释放（CICR）放大。与此形成鲜明对比的是，通过内核体靶向的TPC1释放钙只诱导了空间受限的钙信号，这些信号不被内质网的CICR放大。这些发现为细胞通过连接复合物“过滤”钙信号的机制提供了新的见解，以确定给定信号是保留局部信号还是转换为传播的全局信号。本质上，核内体和溶酶体代表囊状钙储存，与内质网完全不同，tpc本身不支持CICR，因此也不支持再生钙波的传播。因此，通过TPCs的“定量”囊泡钙释放必须随后通过CICR招募内质网上的肌醇1,4,5-三磷酸受体和/或红嘌呤受体，以引起钙波的传播。这可能需要对目前关于细胞内钙信号传导机制的观点进行修订。因此，本综述的目的是为这一领域的未来研究提供一个适当的框架。
Recently, we identified, for the first time, two-pore channels (TPCs, TPCN for gene name) as a novel family of nicotinic acid adenine dinucleotide phosphate (NAADP)-gated, endolysosome-targeted calcium release channels. Significantly, three subtypes of TPCs have been characterized, TPC1-3, with each being targeted to discrete acidic calcium stores, namely lysosomes (TPC2) and endosomes (TPC1 and TPC3). That TPCs act as NAADP-gated calcium release channels is clear, given that NAADP binds to high- and low-affinity sites associated with TPC2 and thereby induces calcium release and homologous desensitization, as observed in the case of endogenous NAADP receptors. Moreover, NAADP-evoked calcium signals via TPC2 are ablated by short hairpin RNA knockdown of TPC2 and by depletion of acidic calcium stores with bafilomycin. Importantly, however, NAADP-evoked calcium signals were biphasic in nature, with an initial phase of calcium release from lysosomes via TPC2, being subsequently amplified by calcium-induced calcium release (CICR) from the endoplasmic reticulum (ER). In marked contrast, calcium release via endosome-targeted TPC1 induced only spatially restricted calcium signals that were not amplified by CICR from the ER. These findings provide new insights into the mechanisms that cells may utilize to “filter” calcium signals via junctional complexes to determine whether a given signal remains local or is converted into a propagating global signal. Essentially, endosomes and lysosomes represent vesicular calcium stores, quite unlike the ER network, and TPCs do not themselves support CICR or, therefore, propagating regenerative calcium waves. Thus “quantal” vesicular calcium release via TPCs must subsequently recruit inositol 1,4,5-trisphoshpate receptors and/or ryanodine receptors on the ER by CICR to evoke a propagating calcium wave. This may call for a revision of current views on the mechanisms of intracellular calcium signaling. The purpose of this review is, therefore, to provide an appropriate framework for future studies in this area.
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影响因子：
20.1
作者：
Boittin, FX;Galione, A;Evans, AM
通讯作者：
Evans, AM
影响因子：
4
作者：
Berridge, Michael J.
通讯作者：
Berridge, Michael J.
影响因子：
4.4
作者：
de Brito, Olga Martins;Scorrano, Luca
通讯作者：
Scorrano, Luca
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
DOI：
10.1083/jcb.150.3.581
发表时间：
2000-08-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Berg I;Potter BV;Mayr GW;Guse AH
通讯作者：
Guse AH