ArticleThe Journal of biological chemistry2010
Natural and engineered photoactivated nucleotidyl cyclases for optogenetic applications.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 224 citations in OpenAlex.
- Red-Shifted Epac-Based FRET cAMP Sensors for All-Optical cAMP Control and Multiparameter Imaging.Cells · 2026Article
- Global impact on metabolic capacity of yeast cell factories by optogenetic control of the cAMP-PKA axis.Applied and environmental microbiology · 2026Article
- The global patent landscape of optogenetics: current advances, challenges and opportunities.Nature biotechnology · 2026Article
- Identification of Key Residues in Allosteric Signaling of Photoactivated Adenylyl Cyclase.bioRxiv : the preprint server for biology · 2026Article
- A Glial Hub-and-Spoke Circuitry in C. elegans orchestrates bidirectional thermosensation.Nature communications · 2026Article
- Two Decades of Optogenetic Tools: A Retrospective and a Look Ahead.Advanced genetics (Hoboken, N.J.) · 2025Review
- Protein design accelerates the development and application of optogenetic tools.Computational and structural biotechnology journal · 2025Review
- Early-life challenge enhances cortisol regulation in zebrafish larvae.Biology open · 2024Article
- Article
- Neuropeptidergic regulation of neuromuscular signaling in larval zebrafish alters swimming behavior and synaptic transmission.iScience · 2024Article
- An Integrated Optogenetic and Bioelectronic Platform for Regulating Cardiomyocyte Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Light-Mediated Enhancement of Glucose-Stimulated Insulin Release of Optogenetically Engineered Human Pancreatic Beta-Cells.ACS synthetic biology · 2024Article
- ATP-dependent conformational dynamics in a photoactivated adenylate cyclase revealed by fluorescence spectroscopy and small-angle X-ray scattering.Communications biology · 2024Article
- Optogenetic elevation of postsynaptic cGMP in the hippocampal dentate gyrus enhances LTP and modifies mouse behaviors.Frontiers in molecular neuroscience · 2024Article
- Article
- An Integrated Optogenetic and Bioelectronic Platform for Regulating Cardiomyocyte Function.bioRxiv : the preprint server for biology · 2023Article
- Cardiac optogenetics: shining light on signaling pathways.Pflugers Archiv : European journal of physiology · 2023Review
- Article
- The Caenorhabditis elegans innexin INX-20 regulates nociceptive behavioral sensitivity.Genetics · 2023Article
- Precise modulation of embryonic development through optogenetics.Genesis (New York, N.Y. : 2000) · 2022Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cyclic nucleotides, cAMP and cGMP, are ubiquitous second messengers that regulate metabolic and behavioral responses in diverse organisms. We describe purification, engineering, and characterization of photoactivated nucleotidyl cyclases that can be used to manipulate cAMP and cGMP levels in vivo. We identified the blaC gene encoding a putative photoactivated adenylyl cyclase in the Beggiatoa sp. PS genome. BlaC contains a BLUF domain involved in blue-light sensing using FAD and a nucleotidyl cyclase domain. The blaC gene was overexpressed in Escherichia coli, and its product was purified. Irradiation of BlaC in vitro resulted in a small red shift in flavin absorbance, typical of BLUF photoreceptors. BlaC had adenylyl cyclase activity that was negligible in the dark and up-regulated by light by 2 orders of magnitude. To convert BlaC into a guanylyl cyclase, we constructed a model of the nucleotidyl cyclase domain and mutagenized several residues predicted to be involved in substrate binding. One triple mutant, designated BlgC, was found to have photoactivated guanylyl cyclase in vitro. Irradiation with blue light of the E. coli cya mutant expressing BlaC or BlgC resulted in the significant increases in cAMP or cGMP synthesis, respectively. BlaC, but not BlgC, restored cAMP-dependent growth of the mutant in the presence of light. Small protein sizes, negligible activities in the dark, high light-to-dark activation ratios, functionality at broad temperature range and physiological pH, as well as utilization of the naturally occurring flavins as chromophores make BlaC and BlgC attractive for optogenetic applications in various animal and microbial models.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.