Department of Pharmacology, Cambridge CB2 1PD, UK.
Mol Cell Endocrinol. 2012 Apr 28;353(1-2):21-8. doi: 10.1016/j.mce.2011.08.028. Epub 2011 Aug 25.
The Ca(2+) signals that control almost every cellular activity are generated by regulating Ca(2+) transport, usually via Ca(2+)-permeable channels, across the plasma membrane or the membranes of intracellular organelles. The most widespread and best understood of the intracellular Ca(2+) channels are inositol trisphosphate receptors (IP(3)R) and ryanodine receptors, most of which are expressed in the endoplasmic or sarcoplasmic reticulum. However, accumulating evidence suggests physiological roles for many additional Ca(2+) channels in both ER and other intracellular organelles. Interactions between these channels, whether mediated by Ca(2+) itself or interactions between proteins, is a recurrent feature of the Ca(2+) signals evoked by physiological stimuli. We focus on two specific examples, clustering of IP(3)Rs and NAADP (nicotinic acid dinucleotide phosphate)-evoked Ca(2+) release from endo-lysosomes, to illustrate the diversity of Ca(2+) channels and the interplay between them.
控制几乎所有细胞活动的 Ca(2+)信号是通过调节 Ca(2+)跨质膜或细胞内细胞器膜的运输产生的，通常是通过 Ca(2+)-通透通道。细胞内 Ca(2+)通道中最广泛和最被理解的是肌醇三磷酸受体 (IP(3)R)和 Ryanodine 受体，其中大多数在内质网或肌浆网上表达。然而，越来越多的证据表明，许多其他 Ca(2+)通道在 ER 和其他细胞内细胞器中具有生理作用。这些通道之间的相互作用，无论是由 Ca(2+)本身介导还是由蛋白质之间的相互作用介导，都是生理刺激引起的 Ca(2+)信号的一个反复出现的特征。我们将重点介绍两个具体的例子，即 IP(3)R 的聚集和 NAADP（烟酰胺二核苷酸磷酸）引发的内体溶酶体 Ca(2+)释放，以说明 Ca(2+)通道的多样性及其相互作用。
