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Optogenetics is a method that uses light to control cellular events. Applications of optogenetics include manipulation of an action potential,1  translocation of a protein of interest to cellular compartments,2  oligomerization-mediated activation of cellular signaling3  and regulation of protein function by the uncaging of activation domains.4  Photosensory proteins are used in the optogenetic system, where they absorb light and undergo a conformational change. Protein–protein interactions serve as a fundamental motif in cellular signal transduction. Therefore, light-inducible dimers are useful for controlling the protein function in a signaling pathway. Representatives of light-inducible dimers include the cryptochrome 2 (Cry2) and cryptochrome-interacting basic helix–loop–helix 1 (Cib1) pair, the iLID system,5  the Magnets6  for blue light-absorbing photosensory proteins and phytochrome B (PhyB) and phytochrome-interacting factor (Pif) pair for a red light-absorbing system.7  Recently, an infrared optogenetic dimerization system using bacterial phytochrome was developed,8,9  further expanding the available spectra for optogenetic tool development. Each system has a unique property, especially in the temporal kinetics of association and dissociation, and which is used in the perturbation of signaling pathways. Because of the high spatiotemporal delivery of incident light, optogenetic tools have benefits for revealing cellular functions that require analysis of spatial and temporal regulation.10  The applicability of spatial and temporal regulation by optogenetics is highlighted in a study that applied an optogenetic son of sevenless (optoSOS) system to elucidate intercellular propagation of the Erk signaling by single-cell specific activation and also to show activation frequency-dependent regulation of downstream gene expression.11  The capabilities of optogenetics to manipulate widely diverse cellular events with high spatiotemporal resolution serve as effective tools for the analysis of cellular signaling pathways that conventional techniques such as chemical stimulation or microfluidic activation cannot achieve.

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