Induction of Signal Transduction by Using Non‐Channelrhodopsin‐Type Optogenetic Tools

Abstract

Signal transductions are the basis for all cellular functions. Previous studies investigating signal transductions mainly relied on pharmacological inhibition, RNA interference, and constitutive active/dominant negative protein expression systems. However, such studies do not allow the modulation of protein activity with high spatial and temporal precision in cells, tissues, and organs in animals. Recently, non-channelrhodopsin-type optogenetic tools for regulating signal transduction have emerged. These photoswitches address several disadvantages of previous techniques, and allow us to control a variety of signal transductions such as cell membrane dynamics, calcium signaling, lipid signaling, and apoptosis. In this review we summarize recent advances in the development of such photoswitches and in how these optotools are applied to signaling processes.

Blue-Light Receptors for Optogenetics

“…In combination with the ongoing revolutionary success of optogenetics in the neurosciences, 79,80 these findings provided the impetus for researchers to explore how other protein activities might be subjected to light control in genetically encodable fashion. 67,81–89 As we illustrate in this and the ensuing section 4., the engineering of light-regulated protein actuators that serve as tools in optogenetics has been nothing but amazingly successful. Section 3.1. considers the principal and most successful design strategies which have spawned the plethora of optogenetic actuators now available for controlling cellular metabolism and parameters (cf.…”

“…Specifically, the intrinsic modularity and mechanistic versatility of BL-sensitive photoreceptors, together with the ubiquitous availability of flavins in vivo, make these photoreceptors invaluable tools for a growing number of applications, including light-controlled gene expression, gene modification, protein activity and localization, and regulation of signaling networks. 67,81–89 Compared to the membrane-embedded rhodopsins, soluble photoreceptors necessitate different engineering strategies for optogenetics (Fig. 5), 67,81,85 on account of differences in their modular organization 16 and allosteric signaling mechanisms.…”

“…To this end, a small set of naturally-occurring photoreceptors with immediate optogenetic applicability have been complemented by a much larger suite of engineered photoreceptors devised by the strategies covered in section 3. 67,81–89 To date, these engineering efforts have been most successful with blue-light-sensitive photoreceptors, particularly in the cryptochrome and LOV classes. As discussed in this section, natural and engineered UV- and BL-sensitive photoreceptors together have now unlocked numerous cellular parameters and processes for optogenetic intervention, including protein-protein interactions, transcription (sec.…”

“…Aside from earlier work on PYP, these studies provided the first atomic view of how light signals are detected by a soluble, autonomously assembling photoreceptor and translated into protein structural transitions, here the reversible unfolding of the ancillary Jα helix of the LOV photosensor. In combination with the ongoing revolutionary success of optogenetics in the neurosciences, , these findings provided the impetus for researchers to explore how other protein activities might be subjected to light control in genetically encodable fashion. ,− As we illustrate in this and the ensuing section , the engineering of light-regulated protein actuators that serve as tools in optogenetics has been nothing but amazingly successful. Section considers the principal and most successful design strategies which have spawned the plethora of optogenetic actuators now available for controlling cellular metabolism and parameters (cf.…”

Membrane Dynamics Induced by a Phosphatidylinositol 3,4,5-Trisphosphate Optogenetic Tool

“…Recently, optogenetic approaches using photoreceptors derived from plants, fungi, and bacteria have emerged. 17 Several photoreceptors, including phototropin1, cryptochrome 2 (CRY2), and phytochrome B (PhyB), have been harnessed as photoswitches, and they have also been intensively engineered. We have developed several optogenetic tools for apoptosis based on Vivid, a fungal blue-light photoreceptor, 18 PhyB-PIF6-based G protein-coupled receptors, 19 a transcription system based on the CRY2-CIB1 system, 20 and the Magnet system 21 that we developed from Vivid.…”