Department of Molecular Biology, Princeton University, Princeton NJ 08544, United States.
Department of Molecular Biology, Princeton University, Princeton NJ 08544, United States.
Curr Opin Chem Biol. 2019 Feb;48:106-113. doi: 10.1016/j.cbpa.2018.11.010. Epub 2018 Dec 5.
Cells sense, process, and respond to extracellular information using signaling networks: collections of proteins that act as precise biochemical sensors. These protein networks are characterized by both complex temporal organization, such as pulses of signaling activity, and by complex spatial organization, where proteins assemble structures at particular locations and times within the cell. Yet despite their ubiquity, studying these spatial and temporal properties has remained challenging because they emerge from the entire protein network rather than a single node, and cannot be easily tuned by drugs or mutations. These challenges are being met by a new generation of optogenetic tools capable of directly controlling the activity of individual signaling nodes over time and the assembly of protein complexes in space. Here, we outline how these recent innovations are being used in conjunction with engineering-influenced experimental design to address longstanding questions in signaling biology.
细胞利用信号网络感知、处理和响应细胞外信息：这些蛋白质网络作为精确的生化传感器，起着信号转导的作用。这些蛋白网络的特点是具有复杂的时间组织，如信号活动的脉冲，以及复杂的空间组织，其中蛋白质在细胞内的特定位置和时间组装结构。然而，尽管它们无处不在，但研究这些时空特性仍然具有挑战性，因为它们是由整个蛋白质网络而不是单个节点产生的，并且不能通过药物或突变轻易调节。新一代的光遗传学工具能够直接控制单个信号节点随时间的活性和蛋白质复合物在空间中的组装，正在应对这些挑战。在这里，我们概述了这些最新的创新技术如何与工程影响的实验设计相结合，来解决信号生物学中的长期问题。
