Light-activated receptor tyrosine kinases: Designs and applications

Crossman, Samuel H.; Janovjak, Harald

doi:10.1016/j.coph.2022.102197

Cited by 4 publications

(4 citation statements)

References 62 publications

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“…Point substitution R599E (numbered relative to the start codon of the fusion receptor) was introduced in MSMEG_2027-FGFR1 using site-directed mutagenesis PCR (oligonucleotides 7 and 8, Supplementary Table S3 ). The charge inversion substitution (R195E in full length murine FGFR1; R599E in our fusion receptor) prevents formation of a functionally essential, asymmetric kinase domain dimer in FGFR1 [43] and was used as a probe for dimer formation during receptor signalling as demonstrated previously [4, 42].…”

Section: Methodsmentioning

confidence: 99%

“…In particular, chemogenetic tools utilise small molecules as interaction regulators, which can be applied over prolonged periods of time, whereas optogenetic tools respond to light triggers, which are beneficial for fast and local control. A number of available chemogenetic tools to induce protein homo-or heterodimerization have now been applied in dozens of in vitro and in vivo studies, including on signalling dynamics [1][2][3][4], protein expression [5], enzyme activity [6,7], histone modification [8], and even as chemically inducible "kill switches" in human cell therapy [9,10].…”

Section: Introductionmentioning

confidence: 99%

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A F₄₂₀-dependent single domain chemogenetic tool for protein de-dimerization

Antoney

Kainrath

Ahmed

et al. 2022

Preprint

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Protein-protein interactions (PPIs) mediate many fundamental cellular processes and their control through optically or chemically responsive protein domains has a profound impact on basic research and some clinical applications. Most available chemogenetic methods induce the association, i.e., dimerization or oligomerization, of target proteins, and the few available dissociation approaches either break large oligomeric protein clusters or heteromeric complexes. Here, we have exploited the controlled dissociation of a dimeric oxidoreductase from mycobacteria (MSMEG_2027) by its native cofactor, F420, which is not present in mammals, as a bioorthogonal monomerization switch. We found that in the absence of F420, MSMEG_2027 forms a unique domain-swapped dimer that occludes the cofactor binding site. Substantial remodelling of the intertwined N-terminal helix upon F420 binding results in the dissolution of the dimer. We then show that MSMEG_2027 can be expressed as fusion proteins in human cells and apply it as a tool to induce and release MAPK/ERK signalling downstream of a chimeric fibroblast growth factor receptor 1 (FGFR1) tyrosine kinase. This F420-dependent chemogenetic de-dimerization tool is stoichiometric, based on a single domain and presents a novel mechanism to investigate protein complexes in situ.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A F₄₂₀-dependent single domain chemogenetic tool for protein de-dimerization

Antoney

Kainrath

Ahmed

et al. 2022

Preprint

Self Cite

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“…In an alternative approach, endogenous metabotropic GPCRs can be rendered light sensitive by genetic code expansion and chemical conjugation of a photo-responsive group. 148 , 149 These approaches are again not limited to classical ionotropic and metabotropic neuromodulation but can, in principle, apply to any light-activated receptor to trigger intracellular signaling cascades 150 – 152 that modify the cytoskeleton, apoptosis, or neurogenesis. However, many of these tools require high illumination intensities to activate the photosensitive protein (Box 2) or photons in the violet spectrum to trigger the conformational changes of a photoswitch.…”

Section: Future Directionsmentioning

confidence: 99%

Bioluminescence as a functional tool for visualizing and controlling neuronal activity in vivo

Porta-de-la-Riva,

Morales-Curiel,

Carolina Gonzalez

et al. 2024

Neurophoton.

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. The use of bioluminescence as a reporter for physiology in neuroscience is as old as the discovery of the calcium-dependent photon emission of aequorin. Over the years, luciferases have been largely replaced by fluorescent reporters, but recently, the field has seen a renaissance of bioluminescent probes, catalyzed by unique developments in imaging technology, bioengineering, and biochemistry to produce luciferases with previously unseen colors and intensity. This is not surprising as the advantages of bioluminescence make luciferases very attractive for noninvasive, longitudinal in vivo observations without the need of an excitation light source. Here, we review how the development of dedicated and specific sensor-luciferases afforded, among others, transcranial imaging of calcium and neurotransmitters, or cellular metabolites and physical quantities such as forces and membrane voltage. Further, the increased versatility and light output of luciferases have paved the way for a new field of functional bioluminescence optogenetics, in which the photon emission of the luciferase is coupled to the gating of a photosensor, e.g., a channelrhodopsin and we review how they have been successfully used to engineer synthetic neuronal connections. Finally, we provide a primer to consider important factors in setting up functional bioluminescence experiments, with a particular focus on the genetic model Caenorhabditis elegans , and discuss the leading challenges that the field needs to overcome to regain a competitive advantage over fluorescence modalities. Together, our paper caters to experienced users of bioluminescence as well as novices who would like to experience the advantages of luciferases in their own hand.

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“…52−54 Certain proteins such as the light-oxygen-voltage-sensing domains (LOV domains), chryptochromes (CRY2), and phytochromes (PHYB) change their conformations when exposed to light and undergo dimerization or oligomerization with their specific binding partners (light induced/light activated dimerization, LID/LAD). 55 While these proteins naturally participate in cellular activities like phototropism and circadian rhythms, they are now extensively used by chemical biologists to study activities dependent on protein density. LOV and CRY2 domains require flavin cofactor (abundantly available in all cells) and respond to blue light.…”

Section: Regulating Activity Through Noncovalent Interactions and Con...mentioning

confidence: 99%

Strategies for Conditional Regulation of Proteins

Nadendla

Simpson

Becher

et al. 2023

JACS Au

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Design of the next-generation of therapeutics, biosensors, and molecular tools for basic research requires that we bring protein activity under control. Each protein has unique properties, and therefore, it is critical to tailor the current techniques to develop new regulatory methods and regulate new proteins of interest (POIs). This perspective gives an overview of the widely used stimuli and synthetic and natural methods for conditional regulation of proteins.

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Light-activated receptor tyrosine kinases: Designs and applications

Cited by 4 publications

References 62 publications

A F₄₂₀-dependent single domain chemogenetic tool for protein de-dimerization

A F₄₂₀-dependent single domain chemogenetic tool for protein de-dimerization

Bioluminescence as a functional tool for visualizing and controlling neuronal activity in vivo

Strategies for Conditional Regulation of Proteins

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Light-activated receptor tyrosine kinases: Designs and applications

Cited by 4 publications

References 62 publications

A F420-dependent single domain chemogenetic tool for protein de-dimerization

A F420-dependent single domain chemogenetic tool for protein de-dimerization

Bioluminescence as a functional tool for visualizing and controlling neuronal activity in vivo

Strategies for Conditional Regulation of Proteins

Contact Info

Product

Resources

About

A F₄₂₀-dependent single domain chemogenetic tool for protein de-dimerization

A F₄₂₀-dependent single domain chemogenetic tool for protein de-dimerization