Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Mol Cell. 2013 Jan 24;49(2):322-30. doi: 10.1016/j.molcel.2012.11.003. Epub 2012 Dec 6.
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.
哺乳动物细胞对外界信息的处理通常涉及到信号分子和转录因子的看似冗余的同工型。理解对同一信号做出响应并控制一组共享基因的共表达同工型的功能相关性仍然有限。在这里,我们使用单个活哺乳动物细胞的成像显示,密切相关的转录因子 NFAT1 和 NFAT4 在响应细胞刺激时具有不同的核定位动力学。NFAT4 表现出快速的反应,具有快速随机的核定位爆发。爆发频率随信号水平增长,而响应幅度是固定的。相比之下,NFAT1 具有缓慢的连续反应,其幅度随信号水平增加。这些在单细胞中观察到的不同动力学特征在细胞群体水平上转化为不同的脉冲响应策略。我们认为,看似冗余基因的动态响应多样性可以为细胞提供增强的时间信息处理能力。