At Light Speed: Advances in Optogenetic Systems for Regulating Cell Signaling and Behavior

Repina, Nicole; Rosenbloom, Alyssa B.; Mukherjee, Abhirup; Schaffer, David V.; Kane, Ravi S.

doi:10.1146/annurev-chembioeng-060816-101254

Cited by 141 publications

(135 citation statements)

References 143 publications

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“…Optogenetic tools for cell biological applications , Ravi S. Kane 1 The key drawback of the Cry2PHR/CIBN system is that phototoxicity of blue light can limit its application in vivo.…”

Section: Editorialmentioning

confidence: 99%

“…Key signaling pathways involved in cell proliferation, tumorigenesis and inflammation (e.g., the Ras/Raf/Mek/Erk cascade, Wnt pathway, PI3K/Akt pathway) have been optogenetically controlled in numerous cell types (1). Many more pathways can be controlled by engineering new optogenetic fusions with receptors or signaling domains of interest, activating or de-activating a pathway at a user-defined node in the signaling cascade.…”

Section: Editorialmentioning

confidence: 99%

“…As a proof of principle, Wang et al controlled blood glucose levels in mice using external illumination of optogenetic proteins expressed in the liver (9). Such approaches can be extended to many other organs and biological processes, particularly in light of recent engineering advances in minimally invasive, implantable LED devices (1).…”

Section: Editorialmentioning

confidence: 99%

“…In contrast to traditional approaches for controlling cell signaling, such as gene overexpression or the use of soluble agonists, the field of optogenetics uses light-responsive proteins to control the activity of a desired signaling protein. The advantage of using light is that the timing, location, and intensity of the signal can be dynamically and precisely controlled using optics (1). Furthermore, unlike small molecules or purified proteins used in cell signaling studies, optogenetic techniques have reduced off-target effects and are relatively inexpensive, as light can be easily generated by a light source such as a light-emitting diode (LED) or laser.…”

mentioning

confidence: 99%

“…The subsequent development of various non-opsin based optogenetic systems has allowed researchers to use lightsensitive protein-protein interactions to modulate cellular activities (1). The tools in this category can be broadly categorized into dimerizers and oligomerizers.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Optogenetic tools for cell biological applications

Mukherjee¹,

Repina²,

Schaffer³

et al. 2017

J. Thorac. Dis.

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“…Optogenetic tools for cell biological applications , Ravi S. Kane 1 The key drawback of the Cry2PHR/CIBN system is that phototoxicity of blue light can limit its application in vivo.…”

Section: Editorialmentioning

confidence: 99%

Section: Editorialmentioning

confidence: 99%

Section: Editorialmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Optogenetic tools for cell biological applications

Mukherjee¹,

Repina²,

Schaffer³

et al. 2017

J. Thorac. Dis.

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Near‐Infrared Manipulation of Membrane Ion Channels via Upconversion Optogenetics

Wang

et al. 2018

Adv. Biosys.

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Membrane ion channels are ultimately responsible for the propagation and integration of electrical signals in the nervous, muscular, and other systems. Their activation or malfunctioning plays a significant role in physiological and pathophysiological processes. Using optogenetics to dynamically and spatiotemporally control ion channels has recently attracted considerable attention. However, most of the established optogenetic tools (e.g., channelrhodopsins, ChRs) for optical manipulations, are mainly stimulated by UV or visible light, which raises the concerns of potential photodamage, limited tissue penetration, and high‐invasive implantation of optical fiber devices. Near‐infrared (NIR) upconversion nanoparticle (UCNP)‐mediated optogenetic systems provide great opportunities for overcoming the problems encountered in the manipulation of ion channels in deep tissues. Hence, this review focuses on the recent advances in NIR regulation of membrane ion channels via upconversion optogenetics in biomedical research. The engineering and applications of upconversion optogenetic systems by the incorporation multiple emissive UCNPs into various light‐gated ChRs/ligands are first elaborated, followed by a detailed discussion of the technical improvements for more precise and efficient control of membrane channels. Finally, the future perspectives for refining and advancing NIR‐mediated upconversion optogenetics into in vivo even in clinical applications are proposed.

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Single‐Component Optogenetic Tools for Inducible RhoA GTPase Signaling

et al. 2021

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to the extracellular matrix (ECM) via focal adhesions. [3] Thus, new tools for inducible control over RhoA activity may greatly enhance understanding of cytoskeletal dynamics and mechanotransduction. [4,5] Optogenetics is highly attractive for this purpose owing to its high spatiotemporal precision versus pharmacological and genetic techniques that can be encumbered by slow uptake/washout kinetics and pleotropic effects. Because small GTPases and their activating guanine nucleotide exchange factors (GEFs) signal at the plasma membrane, optogenetic membrane localization techniques are effective for inducible control over their function, where cytosol-sequestered proteins are dynamically recruited to the cytosol-facing inner leaflet of the plasma membrane to upregulate their signaling. [6] Based on earlier reported chemically inducible dimerization (CID)-based approaches for RhoA membrane recruitment, [7,8] optogenetic heterodimerization and photoactivatable chemically induced dimerization between a photo-responsive protein and a protein-binding partner (one of which is membrane localized) have been widely used to control upstream RhoA-activating GEFs [9][10][11][12][13][14] and phosphatases. [15] The heterodimerization strategy is sensitive to the stoichiometry of the two components, and thus may require expression leveltuning by clonal cell line selection and/or multiple fluorescent tags (i.e., separate for each component) at the expense of optical bandwidth otherwise useful for visualizing other fluorescent probes. [16][17][18] Previously, we reported the direct optogenetic control over RhoA GTPase itself by another mechanism of inducible clustering of RhoA fused to an oligomerizing form of plant cryptochrome, which presumably increases the binding avidity of the GTPase to membrane GEFs. However, this system has limited spatial resolution due to extensive cytosolic diffusion beyond the optical stimulation field prior to stable membrane localization post-oligomerization. [19] Recently, we reported that BcLOV4, a light-oxygen-voltage (LOV) flavoprotein from Botrytis cinerea, rapidly translocates to the plasma membrane in mammalian cells via a blue lightregulated electrostatic protein-lipid interaction (PLI) with the inner leaflet. [20,21] This direct interaction with the membrane itself is powerful for creating "single-component" tools for dynamic membrane recruitment of fused peripheral membrane proteins, without the obligate heterodimerization-or Optogenetic tools are created to control RhoA GTPase, a central regulator of actin organization and actomyosin contractility. RhoA GTPase, or its upstream activator ARHGEF11, is fused to BcLOV4, a photoreceptor that can be dynamically recruited to the plasma membrane by a light-regulated protein-lipid electrostatic interaction with the inner leaflet. Direct membrane recruitment of these proteins induces potent contractile signaling sufficient to separate adherens junctions with as little as one pulse of blue light. Induced cytoskeletal morphology changes are dependent o...

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At Light Speed: Advances in Optogenetic Systems for Regulating Cell Signaling and Behavior

Cited by 141 publications

References 143 publications

Optogenetic tools for cell biological applications

Optogenetic tools for cell biological applications

Near‐Infrared Manipulation of Membrane Ion Channels via Upconversion Optogenetics

Single‐Component Optogenetic Tools for Inducible RhoA GTPase Signaling

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