Hormone-induced secretory and nuclear translocation of calmodulin:: Oscillations of calmodulin concentration with the nucleus as an integrator
Hormone-induced secretory and nuclear translocation of calmodulin:: Oscillations of calmodulin concentration with the nucleus as an integrator
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DOI：
10.1073/pnas.96.8.4426
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发表时间：
1999-04-13
影响因子：
11.1
通讯作者：
Tepikin, AV
中科院分区：
文献类型：
--
作者：
Craske, H;Takeo, T;Tepikin, AV
许多重要的酶活性都受钙离子依赖的钙调蛋白(CaM)相互作用的调节，一些最重要的CaM作用靶点在细胞核内，已有报道钙离子依赖的CaM转位到这个细胞器中，激素诱导的胞内钙信号在生理上以振荡的形式发生，但到目前为止，CaM浓度的振荡还没有被描述。我们将荧光标记的CaM装载到胰腺腺泡细胞中，并通过共聚焦显微镜监测不同区域的荧光。持续高浓度的激素CCK或神经递质乙酰胆碱引起胞质CaM从基底层非核区进入分泌颗粒区的短暂运动，此后，CaM移位到核质中约占结合钙的50%，在较低的激素浓度下，引起Ca~(2+)振荡，在分泌颗粒区可见CaM浓度升高的规律性尖峰，而在基底非核区CaM浓度下降的镜像尖峰。细胞核能够整合钙离子尖峰引起的CaM易位的脉冲，从而使该蛋白的核质浓度持续升高。
Many important enzyme activities are regulated by Ca2+-dependent interactions with calmodulin (CaM), Some of the most important targets for CaM action are in the nucleus, and Ca2+-dependent CaM translocation into this organelle has been reported, Hormone-evoked cytosolic Ca2+ signals occur physiologically as oscillations, but, so far, oscillations in CaM concentration have not been described. We loaded fluorescent-labeled CaM into pancreatic acinar cells and monitored the fluorescence in various regions by confocal microscopy. Sustained high concentrations of the hormone cholecystokinin or the neurotransmitter acetylcholine evoked a transient movement of cytosolic CaM from the basal nonnuclear area into the secretory granule region and, thereafter, a more substantial and prolonged translocation of CaM into the nucleoplasm About 50% of the CaM that bound Ca2+ translocated, At a lower hormone concentration, evoking Ca2+ oscillations, regular spikes of increased CaM concentration were seen in the secretory granule region with mirror image spikes of decreased CaM concentration in the basal nonnuclear region. The nucleus was able to integrate the Ca2+ spike-evoked pulses of CaM translocation into a sustained elevation of the nucleoplasmic concentration of this protein.