2014 年 134 巻 5 号 p. 647-654
Complexity in signaling networks is often derived from co-opting particular sets of molecules for multiple operations. Understanding how cells achieve such sophisticated processing using a finite set of molecules within a confined space - what we call the “signaling paradox”- is critical to cell biology and bioengineering as well as the emerging field of synthetic biology. We have recently developed a series of chemical-molecular tools that allow for inducible, quick-onset and specific perturbation of various signaling molecules. The present technique has been employed to unravel several important, previously unresolved questions regarding the regulatory mechanisms of potassium ion channels, the membrane targeting mechanisms of small GTPases and positive feedback machinery in neutrophil migration. Using this novel technique in conjunction with conventional fluorescence imaging and biochemical analysis, we are currently further dissecting intricate signaling networks in living cells. Ultimately, we will generate completely orthogonal machinery in cells to achieve existing, as well as novel, cellular functions. Our synthetic, multidisciplinary approach will elucidate the signaling paradox in cells created by nature.