la Cour Jonas M, Mollerup Jens, Berchtold Martin Werner
Department of Molecular Biology, University of Copenhagen, Copenhagen, Denmark.
Biochem Biophys Res Commun. 2007 Feb 23;353(4):1063-7. doi: 10.1016/j.bbrc.2006.12.143. Epub 2006 Dec 27.
A variety of stimuli can trigger intracellular calcium oscillations. Relatively little is known about the molecular mechanisms decoding these events. We show that ALG-2, a Ca2+-binding protein originally isolated as a protein associated with apoptosis, is directly linked to Ca2+ signalling. We discovered that the subcellular distribution of a tagged version of ALG-2 could be directed by physiological external stimuli (including ATP, EGF, prostaglandin, histamine), which provoke intracellular Ca2+ oscillations. Cellular stimulation led to a redistribution of ALG-2 from the cytosol to a punctate localization in an oscillatory fashion unitemporally with Ca2+ oscillations, whereas a Ca2+-binding deficient mutant of ALG-2 did not redistribute. Using tagged ALG-2 as bait we identified its novel target protein Sec31A and based on the partial colocalization of endogenous ALG-2 and Sec31A we propose that ALG-2 temporarily binds to the COPII vesicles providing a link between Ca2+ signalling and ER to Golgi trafficking.
多种刺激可触发细胞内钙振荡。关于解码这些事件的分子机制，人们了解得相对较少。我们发现，ALG-2是一种最初作为与细胞凋亡相关的蛋白质而分离出的钙结合蛋白，它与钙信号直接相关。我们发现，带有标签的ALG-2的亚细胞分布可由生理外部刺激（包括ATP、表皮生长因子、前列腺素、组胺）来引导，这些刺激会引发细胞内钙振荡。细胞刺激导致ALG-2从细胞质重新分布到点状定位，其方式与钙振荡同步振荡，而ALG-2的钙结合缺陷突变体则不会重新分布。以带有标签的ALG-2为诱饵，我们鉴定出了其新的靶蛋白Sec31A，并基于内源性ALG-2和Sec31A的部分共定位，我们提出ALG-2会暂时与COPII囊泡结合，从而在钙信号与内质网到高尔基体的转运之间建立联系。
