Tanaka Y, Tashjian A H
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3244-8. doi: 10.1073/pnas.92.8.3244.
The ryanodine receptor-like Ca2+ channel (RyRLC) is responsible for Ca2+ wave propagation and Ca2+ oscillations in certain nonmuscle cells by a Ca(2+)-induced Ca2+ release (CICR) mechanism. Cyclic ADP-ribose (cADPR), an enzymatic product derived from NAD+, is the only known endogenous metabolite that acts as an agonist on the RyRLC. However, the mode of action of cADPR is not clear. We have identified calmodulin as a functional mediator of cADPR-triggered CICR through the RyRLC in sea urchin eggs. cADPR-induced Ca2+ release consisted of two phases, an initial rapid release phase and a subsequent slower release. The second phase was selectively potentiated by calmodulin which, in turn, was activated by Ca2+ released during the initial phase. Caffeine enhanced the action of calmodulin. Calmodulin did not play a role in inositol 1,4,5-trisphosphate-induced Ca2+ release. These findings offer insights into the multiple pathways that regulate intracellular Ca2+ signaling.
类兰尼碱受体钙通道(RyRLC)通过钙诱导钙释放(CICR)机制,负责某些非肌肉细胞中的钙波传播和钙振荡。环ADP核糖(cADPR)是一种由NAD+衍生的酶促产物,是已知的唯一一种对RyRLC起激动剂作用的内源性代谢物。然而,cADPR的作用模式尚不清楚。我们已经确定钙调蛋白是海胆卵中通过RyRLC介导cADPR触发的CICR的功能介质。cADPR诱导的钙释放包括两个阶段,一个是初始快速释放阶段,另一个是随后的较慢释放阶段。第二阶段被钙调蛋白选择性增强,而钙调蛋白又被初始阶段释放的钙激活。咖啡因增强了钙调蛋白的作用。钙调蛋白在肌醇1,4,5-三磷酸诱导的钙释放中不起作用。这些发现为调节细胞内钙信号的多种途径提供了见解。