Dynamic Response Diversity of NFAT Isoforms in Individual Living Cells
Dynamic Response Diversity of NFAT Isoforms in Individual Living Cells
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DOI：
10.1016/j.molcel.2012.11.003
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发表时间：
2013-01-24
期刊：
影响因子：
16
通讯作者：
Friedman, Nir
中科院分区：
文献类型：
--
作者：
Yissachar, Nissan;Fischler, Tali Sharar;Friedman, Nir
哺乳动物细胞对外部信息的处理通常涉及信号分子和转录因子的看似冗余的同种型。对响应相同信号并控制一组共享基因的共表达异构体的功能相关性的理解仍然有限。在这里，我们表明，使用个别活的哺乳动物细胞的成像，密切相关的转录因子NFAT 1和NFAT 4具有不同的核定位动态响应细胞刺激。NFAT 4显示出快速反应，具有核定位的快速随机爆发。突发频率随信号电平而增长，而响应幅度是固定的。相比之下，NFAT 1具有缓慢、连续的响应，并且其幅度随着信号电平而增加。这些不同的动力学特征观察到的单细胞转化为不同的脉冲响应策略在细胞群体水平。我们认为，看似冗余的基因的动态响应多样性可以提供细胞增强的时间信息处理能力。
Processing of external information by mammalian cells often involves seemingly redundant isoforms of signaling molecules and transcription factors. Understanding the functional relevance of coexpressed isoforms that respond to the same signal and control a shared set of genes is still limited. Here we show, using imaging of individual living mammalian cells, that the closely related transcription factors NFAT1 and NFAT4 possess distinct nuclear localization dynamics in response to cell stimulation. NFAT4 shows a fast response, with rapid stochastic bursts of nuclear localization. Burst frequency grows with signal level, while response amplitude is fixed. In contrast, NFAT1 has a slow, continuous response, and its amplitude increases with signal level. These diverse dynamical features observed for single cells are translated into different impulse response strategies at the cell population level. We suggest that dynamic response diversity of seemingly redundant genes can provide cells with enhanced capabilities of temporal information processing.