Ca(2+) puffs originate from preestablished stable clusters of inositol trisphosphate receptors.
Ca(2+) puffs originate from preestablished stable clusters of inositol trisphosphate receptors.
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DOI：
10.1126/scisignal.2000466
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发表时间：
2009-11-24
影响因子：
7.3
通讯作者：
Parker I
中科院分区：
文献类型：
--
作者：
Smith IF;Wiltgen SM;Shuai J;Parker I
细胞内的钙信号依赖于内质网膜上三磷酸肌醇受体(IP3Rs)的聚集结构，该受体释放钙离子产生局部信号，称为钙离子喷雾。已经提出了IP3R簇快速组装以响应IP3本身。我们通过使用笼式IP3的闪光光解结合高分辨率钙成像来监测单个IP3R在完整哺乳动物细胞中的活性和定位，从而验证了这一假说。我们的结果表明，在光释放IP3后，潜伏期短至100ms-200ms的喷雾已经涉及几个(n≥4)IP3R通道，并且这个数字随后不会增长。此外，单一活性的IP3R显示出非常有限的能动性，随机模拟表明，通过扩散捕获机制在喷发部位聚集IP3R需要几秒钟的时间。因此，我们没有发现IP3调控的IP3R在完整细胞中快速聚集的证据，而是得出结论，泡芙位点代表预先建立的稳定的IP3R簇，功能IP3R不容易在内质网膜内扩散。
Intracellular Ca2+ signaling crucially depends upon the clustered organization of inositol trisphosphate receptors (IP3Rs) in the ER membrane that liberate Ca2+ to generate local signals known as Ca2+ puffs. Clusters of IP3Rs have been proposed to assemble rapidly in response to IP3 itself. We tested this hypothesis by using flash photolysis of caged IP3 in conjunction with high resolution Ca2+ imaging to monitor the activity and localization of individual IP3Rs within intact mammalian cells. Our results indicate that puffs arising with latencies as short as 100–200 ms following photorelease of IP3 already involve several (n ≥4) IP3R channels, and that this number does not subsequently grow. Moreover, single active IP3Rs show very limited motility, and stochastic simulations suggest that aggregation of IP3Rs at puff sites by a diffusional trapping mechanism would require many seconds. We thus find no evidence for rapid, IP3-regulated clustering of IP3Rs in intact cells, but instead conclude that puff sites represent pre-established, stable clusters of IP3Rs and that functional IP3Rs are not readily diffusible within the ER membrane.
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