Decoding of Cytoplasmic Ca2+ Oscillations through the Spatial Signature Drives Gene Expression
Decoding of Cytoplasmic Ca2+ Oscillations through the Spatial Signature Drives Gene Expression
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DOI：
10.1016/j.cub.2009.03.063
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发表时间：
2009-05-26
期刊：
影响因子：
9.2
通讯作者：
Parekh, Anant B.
中科院分区：
文献类型：
--
作者：
Di Capite, Joseph;Ng, Siaw Wei;Parekh, Anant B.
细胞质Ca 2+振荡是激活许多细胞反应的通用信号传导模式[1，2]。振荡被认为是Ca 2+信号传导的生理机制，因为它们发生在低水平的刺激强度下[3]。Ca 2+振荡被认为是以其振幅和频率传递信息，导致特定下游靶点的激活[4-6]。在这里，我们报告说，振荡内的空间Ca 2+梯度是关键。当质膜Ca 2+外排受到抑制时，在存在外部Ca 2+的情况下，在一系列激动剂浓度范围内引起的肥大细胞中的Ca 2+振荡与不存在Ca 2+的情况下的那些振荡是不可区分的。然而，只有伴随着钙离子通过储存操作的CRAC通道进入的振荡才触发基因表达。增加细胞质Ca 2+缓冲防止振荡，但不基因激活。因此，局部Ca 2+内流而不是全局Ca 2+振荡在生理水平的刺激下驱动基因表达。而不是通过补充商店来维持Ca 2+振荡，我们认为振荡的作用可能是激活CRAC通道，从而确保产生空间限制的生理Ca 2+信号驱动基因激活。此外，我们表明，空间分布的钙离子振荡提供了一种新的机制，即一个多效性信使特异性激活基因表达。
Cytoplasmic Ca2+ oscillations are a universal signaling mode that activates numerous cellular responses [1, 2]. Oscillations are considered the physiological mechanism of Ca2+ signaling because they occur at low levels of stimulus intensity [3]. Ca2+ oscillations are proposed to convey information in their amplitude and frequency, leading to activation of specific downstream targets [4-6]. Here, we report that the spatial Ca2+ gradient within the oscillation is key. Ca2+ oscillations in mast cells evoked over a range of agonist concentrations in the presence of external Ca2+ were indistinguishable from those in the absence of Ca2+ when plasmalemmal Ca2+ extrusion was suppressed. Nevertheless, only oscillations with accompanying Ca2+ entry through store-operated CRAC channels triggered gene expression. Increased cytoplasmic Ca2+ buffering prevented oscillations but not gene activation. Local Ca2+ influx and not global Ca2+ oscillations therefore drives gene expression at physiological levels of stimulation. Rather than serving to maintain Ca2+ oscillations by replenishing stores, we suggest that the role of oscillations might be to activate CRAC channels, thereby ensuring the generation of spatially restricted physiological Ca2+ signals driving gene activation. Furthermore, we show that the spatial profile of a Ca2+ oscillation provides a novel mechanism whereby a pleiotropic messenger specifically activates gene expression.