Tovey S C, Bootman M D, Lipp P, Berridge M J, Bram R J
Laboratory of Molecular Signalling, Babraham Institute, Babraham, Cambridge, CB2 4AT, United Kingdom.
Biochem Biophys Res Commun. 2000 Sep 16;276(1):97-100. doi: 10.1006/bbrc.2000.3442.
The Ca(2+)-modulating cyclophilin ligand (CAML) protein causes stimulation of transcription factors via activation of a store-operated Ca(2+) entry pathway. Since CAML is widely expressed in mammalian tissues, it may be an important regulator of Ca(2+) store function. In the present study, we investigated the consequence of CAML overexpression on Ca(2+) signaling using rapid confocal imaging of Fluo3-loaded NIH3T3 fibroblasts. Control and CAML-expressing cells gave concentration-dependent responses to the Ca(2+) mobilizing agonist ATP. CAML expression reduced the sensitivity of the cells so that higher concentrations of ATP were needed to achieve global Ca(2+) waves. The amplitudes of Ca(2+) waves were significantly reduced in CAML expressing cells, consistent with earlier suggestions that CAML causes depletion of internal Ca(2+) stores. With low ATP concentrations, only local Ca(2+) release events were observed. CAML did not affect the characteristics of these local Ca(2+) signals, suggesting that it does not directly affect Ca(2+) release channels.
钙调节亲环素配体（CAML）蛋白通过激活储存操纵性钙内流途径来刺激转录因子。由于CAML在哺乳动物组织中广泛表达，它可能是钙储存功能的重要调节因子。在本研究中，我们使用装载Fluo3的NIH3T3成纤维细胞的快速共聚焦成像技术，研究了CAML过表达对钙信号的影响。对照细胞和表达CAML的细胞对钙动员激动剂ATP产生浓度依赖性反应。CAML的表达降低了细胞的敏感性，因此需要更高浓度的ATP才能产生全局钙波。在表达CAML的细胞中，钙波的幅度显著降低，这与之前关于CAML导致细胞内钙储存耗竭的观点一致。在低ATP浓度下，仅观察到局部钙释放事件。CAML不影响这些局部钙信号的特征，表明它不直接影响钙释放通道。
