Graduate Program in Neuroscience, Institute for Brain Science and Technology, Inje University, 633-146 Gaegeum 2-dong, Busanjin-gu, Busan 614-735, South Korea.
Neurosci Lett. 2010 Jan 18;469(1):141-4. doi: 10.1016/j.neulet.2009.11.061. Epub 2009 Nov 26.
Cyclin-dependent kinase 5 (Cdk5), which is activated by the non-cyclin regulator p35 or p39, is a proline-directed serine/threonine kinase that is implicated in many physiological and pathological processes. Here, we studied calcium signaling using the fluorescent cytosolic calcium indicator, Fura-4, in NGF-differentiated PC12 cells treated with roscovitine, a Cdk5 inhibitor. As compared to the control cells, the roscovitine-treated cells significantly potentiated intracellular calcium release by membrane depolarization (high K(+)) or through thapsigargin. In addition, roscovitine increased the magnitude of capacitative calcium entry (CCE), i.e., a calcium influx mechanism triggered by the depletion of intracellular calcium stores. Notably, roscovitine markedly slowed the rate of Ca(2+) removal from the plasma membrane. These results suggest that Cdk5 regulates intracellular calcium homeostasis and that the dysregulation of Cdk5 may contribute to disease pathogenesis by perturbing cellular Ca(2+) signaling.
周期蛋白依赖性激酶 5（Cdk5）可被非周期蛋白调节因子 p35 或 p39 激活，是一种脯氨酸导向的丝氨酸/苏氨酸激酶，参与许多生理和病理过程。在这里，我们使用荧光胞质钙离子指示剂 Fura-4 在 NGF 分化的 PC12 细胞中研究了钙信号，这些细胞用 Cdk5 抑制剂罗司维亭处理。与对照细胞相比，罗司维亭处理的细胞通过膜去极化（高 K+）或通过 thapsigargin 显著增强了细胞内钙释放。此外，罗司维亭增加了电容钙内流（CCE）的幅度，即由细胞内钙库耗竭触发的钙内流机制。值得注意的是，罗司维亭明显减缓了 Ca2+从质膜中去除的速度。这些结果表明 Cdk5 调节细胞内钙稳态，Cdk5 的失调可能通过扰乱细胞 Ca2+信号而导致疾病发病机制。
