Distinct roles of inositol 1,4,5-trisphosphate receptor types 1 and 3 in Ca2+ signaling
Distinct roles of inositol 1,4,5-trisphosphate receptor types 1 and 3 in Ca2+ signaling
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DOI：
10.1074/jbc.m311456200
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发表时间：
2004-03-19
影响因子：
4.8
通讯作者：
Mikoshiba, K
中科院分区：
文献类型：
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作者：
Hattori, M;Suzuki, AZ;Mikoshiba, K
肌醇1，4，5-三磷酸受体的三种亚型(IP(3)R1、IP(3)R2和IP(3)R3)钙释放通道具有相同的基本特性，但在调节方面有所不同。它们在多大程度上参与了复杂的钙信号，如钙振荡，在很大程度上仍不清楚。在这里，我们表明，HeLa细胞表达类似数量的IP(3)R1和IP(3)R3，但通过RNA干扰每个亚型的敲除导致了截然不同的钙信号模式。IP(3)R1的敲除显著减少了总的钙信号并终止了钙振荡。相反，与对照组相比，IP(3)R3基因敲除会导致更强劲和更持久的钙振荡。在主要表达IP(3)R3的COS-7细胞中，IP(3)R3基因敲除的效果惊人地相似，这表明IP(3)R3作为一个抗钙振荡单位发挥作用，而不影响钙信号的峰值，而与其相对表达水平无关。因此，IP3R亚型的差异表达对于各种形式的钙信号是至关重要的，尤其是IP(3)R1和IP(3)R3在产生钙振荡方面具有相反的作用。
Three subtypes of inositol 1,4,5-trisphosphate receptor (IP(3)R1, IP(3)R2, and IP(3)R3) Ca2+ release channel share basic properties but differ in terms of regulation. To what extent they contribute to complex Ca2+ signaling, such as Ca2+ oscillations, remains largely unknown. Here we show that HeLa cells express comparable amounts of IP(3)R1 and IP(3)R3, but knockdown by RNA interference of each subtype results in dramatically distinct Ca2+ signaling patterns. Knockdown of IP(3)R1 significantly decreases total Ca2+ signals and terminates Ca2+ oscillations. Conversely, knockdown of IP(3)R3 leads to more robust and long lasting Ca2+ oscillations than in controls. Effects of IP(3)R3 knockdown are surprisingly similar in COS-7 cells that predominantly (> 90% of total IP3R) express IP(3)R3, suggesting that IP(3)R3 functions as an anti-Ca2+-oscillatory unit without contributing to peak amplitude of Ca2+ signals, irrespective of its relative expression level. Therefore, differential expression of the IP3R subtype is critical for various forms of Ca2+ signaling, and, particularly, IP(3)R1 and IP(3)R3 have opposite roles in generating Ca2+ oscillations.