Genetically encoded tools based on luminescent proteins

抄録

In a signal transduction diagram, arrows are generally used to link molecules to show enzymatic reactions and intermolecular interactions. To obtain an exhaustive understanding of a signal transduction system, however, the diagram must contain three axes in space and the time base, because all events are regulated ingeniously in space and time. The scale over time and space is ignored in biochemical approaches in which electrophoresis is applied to a specimen prepared by grinding millions of cells. A farseeing article entitled "Fluorescence Imaging Creates a Window on the Cell" was written by Roger Y. Tsien in 1994, which appeared in Chemical & Engineering News. He advocated employing the so-called real-time and single-cell imaging technique to fully appreciate cell-to-cell heterogeneity. He also had steadfastly pursued the creation of a reliable gate that would enable researchers to better understand the "feelings" of individual cells. Over the past two decades, various genetically encoded probes have been generated using fluorescent and bioluminescent proteins. I will discuss how the probes have advanced our understanding of the spatio-temporal regulation of biological functions, such as cell-cycle progression, autophagy, protein-protein interactions, and metabolism (retinoic acid and bilirubin), inside cells, neurons, embryos, and brains. I will speculate on how these approaches will continue to improve due to the various features of fluorescent/bioluminescent proteins.