Penny Christopher J, Kilpatrick Bethan S, Eden Emily R, Patel Sandip
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
Department of Cell Biology, Institute of Ophthalmology, University College London, London EC1V 9EL, UK.
Cell Calcium. 2015 Oct;58(4):387-96. doi: 10.1016/j.ceca.2015.03.006. Epub 2015 Mar 23.
Acidic organelles such as lysosomes serve as non-canonical Ca(2+) stores. The Ca(2+) mobilising messenger NAADP is thought to trigger local Ca(2+) release from such stores. These events are then amplified by Ca(2+) channels on canonical ER Ca(2+) stores to generate physiologically relevant global Ca(2+) signals. Coupling likely occurs at microdomains formed at membrane contact sites between acidic organelles and the ER. Molecular analyses and computational modelling suggest heterogeneity in the composition of these contacts and predicted Ca(2+) microdomain behaviour. Conversely, acidic organelles might also locally amplify and temper ER-evoked Ca(2+) signals. Ca(2+) microdomains between distinct Ca(2+) stores are thus likely to be integral to the genesis of complex Ca(2+) signals.
酸性细胞器如溶酶体可作为非典型的Ca(2+)储存库。人们认为，Ca(2+)动员信使NAADP会触发此类储存库中局部Ca(2+)的释放。然后，这些事件会通过典型内质网Ca(2+)储存库上的Ca(2+)通道进行放大，以产生具有生理相关性的全局Ca(2+)信号。耦合可能发生在酸性细胞器与内质网之间的膜接触位点形成的微区。分子分析和计算模型表明，这些接触位点的组成存在异质性，并预测了Ca(2+)微区的行为。相反，酸性细胞器也可能在局部放大并调节内质网诱发的Ca(2+)信号。因此，不同Ca(2+)储存库之间的Ca(2+)微区可能是复杂Ca(2+)信号产生所不可或缺的。
