Questioning regulation of two-pore channels by NAADP.
Questioning regulation of two-pore channels by NAADP.
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质疑 NAADP 对双孔通道的调节。
DOI：
10.1166/msr.2013.1027
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Patel,Sandip
中科院分区：
文献类型：
--
作者：
Marchant,JonathanS;Patel,Sandip
NAADP是一种强大的钙离子动员信使。自从1995年NAADP被发现以来，大量的文献表明NAADP将细胞刺激与内溶酶体内钙释放相结合，从而调节了许多细胞功能。然而，对其分子作用机制的定义却远非易事。自2009年以来，随着几个独立的群体联合起来，形成了两孔通道(TPC)家族，作为NAADP激活的通道，对从内酶体钙库中释放钙是必不可少的。然而，这一观点最近受到了挑战，因为有数据清楚地表明，TPC作为钠离子选择性通道发挥作用，显然对NAADP不敏感。鉴于定义离子通道的两个基本特征包括开放刺激和外在离子的性质，对这些看似不可调和的观点的审查是至关重要的。本评论的目的是提炼剩余的共识，同时质疑这些不同的观点。通过这一分析，确定了关键的实验需求。
NAADP is a potent Ca2+ mobilizing messenger. Since its discovery in 1995 a considerable volume of literature has shown that NAADP couples cell stimulation to endolysosomal Ca2+ release and thereby the regulation of many cellular functions. However definition of its molecular mechanism of action has proved far from easy. Since 2009, a consensus emerged as several independent groups coalesced upon the two-pore channel (TPC) family as NAADP-activated channels essential for Ca2+ release from endolysosomal Ca2+ stores. However this view has been recently challenged by data clearly showing that TPCs function as Na+-selective channels apparently insensitive to NAADP. Given the two fundamental characteristics defining an ion channel comprise the opening stimulus and the nature of the permeant ions, scrutiny of these seeming irreconcilable viewpoints is essential. The purpose of this commentary is to distil the remaining consensus while interrogating these divergent viewpoints. From this analysis, critical experimental needs are identified.