Temporal switching and cell-to-cell variability in Ca2+ release activity in mammalian cells.
Temporal switching and cell-to-cell variability in Ca2+ release activity in mammalian cells.
复制标题
哺乳动物细胞中Ca2+释放活性的时间开关和细胞间变异性。
DOI：
10.1038/msb.2009.6
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发表时间：
2009
影响因子：
9.9
通讯作者：
Iino, Masamitsu
中科院分区：
文献类型：
--
作者：
Nakamura, Naotoshi;Yamazawa, Toshiko;Okubo, Yohei;Iino, Masamitsu
关键词：
在统一的外部环境中，遗传上相同的细胞可以表现出不同的表型，这些表型通常被细胞群体平均的常规测量所掩盖。虽然大多数关于这一主题的研究都使用微生物，但很少探索分化的哺乳动物细胞。在这里，我们报告说，只有大约40%的克隆人胚肾293细胞响应与细胞内钙离子的增加时，兰尼碱受体Ca2+释放通道在内质网最大限度地激活咖啡因。Ryanodine受体的表达水平呈单峰分布。我们发现，在咖啡因的敏感性的差异取决于一个关键的平衡之间的Ca2+释放和Ca2+吸收活动，这是放大的再生性质的Ca2+释放机制。此外，个别细胞之间切换的咖啡因敏感和咖啡因不敏感的状态，平均过渡时间约为65小时，提示与咖啡因响应的内源性蛋白质表达水平的时间波动。这些结果表明再生机制的重要性，放大蛋白质表达噪音和诱导细胞间表型变异的哺乳动物细胞。
Genetically identical cells in a uniform external environment can exhibit different phenotypes, which are often masked by conventional measurements that average over cell populations. Although most studies on this topic have used microorganisms, differentiated mammalian cells have rarely been explored. Here, we report that only approximately 40% of clonal human embryonic kidney 293 cells respond with an intracellular Ca2+ increase when ryanodine receptor Ca2+ release channels in the endoplasmic reticulum are maximally activated by caffeine. On the other hand, the expression levels of ryanodine receptor showed a unimodal distribution. We showed that the difference in the caffeine sensitivity depends on a critical balance between Ca2+ release and Ca2+ uptake activities, which is amplified by the regenerative nature of the Ca2+ release mechanism. Furthermore, individual cells switched between the caffeine-sensitive and caffeine-insensitive states with an average transition time of approximately 65 h, suggestive of temporal fluctuation in endogenous protein expression levels associated with caffeine response. These results suggest the significance of regenerative mechanisms that amplify protein expression noise and induce cell-to-cell phenotypic variation in mammalian cells.
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影响因子：
2.9
作者：
Gonze, D;Goldbeter, A
通讯作者：
Goldbeter, A
影响因子：
56.9
作者：
FINCH, EA;TURNER, TJ;GOLDIN, SM
通讯作者：
GOLDIN, SM
DOI：
10.1016/s0006-291x(88)80730-7
发表时间：
1988-04-15
影响因子：
3.1
作者：
IINO, M;KOBAYASHI, T;ENDO, M
通讯作者：
ENDO, M
DOI：
10.1073/pnas.0408507102
发表时间：
2005-03-08
影响因子：
11.1
作者：
Hooshangi, S;Thiberge, S;Weiss, R
通讯作者：
Weiss, R
影响因子：
64.8
作者：
Chang, Hannah H.;Hemberg, Martin;Huang, Sui
通讯作者：
Huang, Sui