Calcium channels are models of self-control.
Calcium channels are models of self-control.
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DOI：
10.1085/jgp.200709786
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发表时间：
2007-05
期刊：
影响因子：
--
通讯作者：
Dunlap K
中科院分区：
文献类型：
--
作者：
Dunlap K
当Ca 2+离子流过单个电压门控Ca 2+通道的孔时，它们会对它们所通过的通道产生反作用，并改变随后的Ca 2+流动。这种局部的、几乎瞬时的调节涉及正反馈和负反馈机制：分别为Ca 2+依赖性易化（CDF）和Ca 2+依赖性失活（CDI）。事实上，某些类型的Ca 2+通道能够经历CDF和CDI，每种形式的调节遵循不同的时间过程，并且对Ca 2+进入的速率、程度和空间定位具有不同的依赖性。这些通道配备了一个特殊的Ca 2+敏感的工具包，它们用来巧妙地操纵自己的Ca 2+内流，从而调节位于Ca 2+进入下游的许多效应器反应。尽管这种自我调节在细胞水平上已经被认识了几十年（Bibram和Eckert，1978; Marban和Tsien，1982），但最近的工作已经开始阐明潜在的分子机制及其内在的复杂性。乔杜里等人(see第385页）为这一发现链增加了几个重要环节。CDF和CDI存在于高电压激活的Cav 1和Cav 2通道的大多数但不是全部成员中，但在低电压激活的Cav 3通道中完全不存在。奇怪的是，尽管CDF和CDI对通道门控和随后的Ca 2+内流的作用完全相反，但它们都是由钙调蛋白（CaM）介导的。重组Cav 1和Cav 2通道的定点诱变表明，CaM与一个典型的“IQ”结构域（所有Cav 1和Cav 2孔形成亚基的细胞质C-末端尾中的高度保守区域）相互作用。去除IQ结构域和阻止CaM结合的IQ结构域中的突变消除了CDF和CDI（Zühlke和罗伊特，1998; Qin等人，1999; Zühlke等人，1999年）。CaM对Ca 2+的高选择性超过Ba 2+（Chao等人，1984）解释了长期公认的Ba 2+不能引起CDF和CDI。虽然乍一看这似乎是一个有限的工具包，但CaM的操作有点像一把满载的瑞士军刀（图1）。
When Ca2+ ions flow through the pore of an individual voltage-gated Ca2+ channel, they act back on the channel they’ve passed through and alter subsequent Ca2+ flow. Such local, almost instantaneous regulation involves both positive and negative feedback mechanisms: Ca2+-dependent facilitation (CDF) and Ca2+-dependent inactivation (CDI), respectively. Indeed, some types of Ca2+ channel are capable of undergoing both CDF and CDI, with each form of modulation following a different time course and having a different dependency on the rate, extent, and spatial localization of Ca2+ entry. These channels are equipped with a special Ca2+-sensitive toolkit, which they use to exquisitely manipulate their own Ca2+ influx, and thereby adjust the many effector responses that lie downstream of the Ca2+ entry. Although such self-regulation has been recognized at the cellular level for decades (Brehm and Eckert, 1978; Marban and Tsien, 1982), recent work has begun to illuminate the underlying molecular mechanisms and their inherent complexity. Chaudhuri et al.(see p. 385 of this issue) have added several essential links to this chain of discovery. CDF and CDI are present in most, but not all, members of the high voltage–activated Cav1 and Cav2 channels, but are entirely absent in the low voltage–activated Cav3 channels. Curiously, despite their diametrically opposite effects on channel gating and consequent Ca2+ influx, both CDF and CDI are mediated by calmodulin (CaM). Site-directed mutagenesis of recombinant Cav1 and Cav2 channels demonstrated that CaM interacts with a canonical “IQ” domain (a highly conserved region in the cytoplasmic C-terminal tail of all Cav1 and Cav2 pore-forming subunits). Removal of the IQ domain and mutations in the IQ domain that prevent CaM binding eliminate both CDF and CDI (Zühlke and Reuter, 1998; Qin et al., 1999; Zühlke et al., 1999). The high selectivity of CaM for Ca2+ over Ba2+(Chao et al., 1984) explains the long-recognized inability of Ba2+ to evoke CDF and CDI. Although at first glance this might seem like a limited toolkit, CaM operates a bit like a fully loaded Swiss Army knife (Fig. 1).
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DOI：
10.1107/s0907444995011826
发表时间：
1996-03-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Rupp, B;Marshak, DR;Parkin, S
通讯作者：
Parkin, S
影响因子：
5.3
作者：
Chaudhuri, D;Chang, SY;Yue, DT
通讯作者：
Yue, DT
影响因子：
5.6
作者：
BABU, YS;BUGG, CE;COOK, WJ
通讯作者：
COOK, WJ
影响因子：
5.7
作者：
Fallon, JL;Halling, DB;Quiocho, FA
通讯作者：
Quiocho, FA
DOI：
10.1073/pnas.262372999
发表时间：
2002-12-24
影响因子：
11.1
作者：
Alseikhan, BA;DeMaria, CD;Yue, DT
通讯作者：
Yue, DT