A hybrid stochastic/deterministic model of single photon response and light adaptation in mouse rods
| Autor: | Sabrina Asteriti, Karl-Wilhelm Koch, Charlotte Johanna Beelen, Daniele Dell'Orco, Lorenzo Cangiano |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
ADP
guanosine-5′-triphosphate completely substituted mutant of rhodopsin SPR Rn activated rhodopsin that has been phosphorylated n times Biochemistry effector of the phototransduction cascade G protein/transducin FFT GPCR Gt photons GC arrestin cyclic nucleotide-gated (channel) time to peak TTP time to peak activated PDE ROS Stochastic simulation Rhodopsin kinase HSDM hybrid stochastic/deterministic model RGS Cascade Transducin Gβγ standard deviation background illumination Visual phototransduction ΔJ photocurrent TTP RGS regulator of G protein signaling Biophysics RK regulator of G protein signaling BG PDE photocurrent ΔU Light adaptation CSM Gα Genetics G protein-coupled receptor GPCR G protein-coupled receptor β- and γ-subunit of the G protein SD Ph cyclic guanosine monophosphate rhodopsin kinase Dynamic modeling Phototransduction Systems biology CSM completely substituted mutant of rhodopsin coefficient of variation multiple photon response Ph photons rhodopsin cGMP cyclic guanosine monophosphate ΔJ GTP TP248.13-248.65 Arr arrestin Rec recoverin Photon MPR genetic structures PDE phosphodiesterase 6 recoverin ΔU photovoltage Gβγ β- and γ-subunit of the G protein phosphodiesterase 6 GDP Structural Biology photovoltage DM hybrid stochastic/deterministic model R rhodopsin Physics Rn biology adenosine-5′-triphosphate adenosine diphosphate GCAPs GCAPs guanylate cyclase-activating proteins HSDM Computer Science Applications FFT fast Fourier-transform guanylate cyclase α-subunit of the G protein Gα α-subunit of the G protein BG background illumination fast Fourier-transform Rhodopsin CNG cyclic nucleotide-gated (channel) SPR single photon response CNG guanylate cyclase-activating proteins CV Arr E effector of the phototransduction cascade activated PDE GC guanylate cyclase Research Article Biotechnology Adaptation (eye) guanosine-5′-diphosphate activated rhodopsin that has been phosphorylated n times deterministic model RK rhodopsin kinase Patch clamp ROS rod outer segment ComputingMethodologies_COMPUTERGRAPHICS GTP guanosine-5′-triphosphate Gt G protein/transducin Rec CV coefficient of variation GDP guanosine-5′-diphosphate ATP adenosine-5′-triphosphate MPR multiple photon response rod outer segment ADP adenosine diphosphate ATP cGMP biology.protein single photon response sense organs DM deterministic model SD standard deviation |
| Zdroj: | Computational and Structural Biotechnology Journal, Vol 19, Iss, Pp 3720-3734 (2021) Computational and Structural Biotechnology Journal |
| ISSN: | 2001-0370 |
| Popis: | Graphical abstract Highlights • A hybrid stochastic/deterministic model of mouse rod phototransduction is presented. • Rod photocurrent to photovoltage conversion in darkness is accurately characterized. • Photoresponses to dim and bright stimuli and in various mutants are well reproduced. • Recently debated molecular mechanisms of the phototransduction cascade are examined. The phototransduction cascade is paradigmatic for signaling pathways initiated by G protein-coupled receptors and is characterized by a fine regulation of photoreceptor sensitivity and electrical response to a broad range of light stimuli. Here, we present a biochemically comprehensive model of phototransduction in mouse rods based on a hybrid stochastic and deterministic mathematical framework, and a quantitatively accurate description of the rod impedance in the dark. The latter, combined with novel patch clamp recordings from rod outer segments, enables the interconversion of dim flash responses between photovoltage and photocurrent and thus direct comparison with the simulations. The model reproduces the salient features of the experimental photoresponses at very dim and bright stimuli, for both normal photoreceptors and those with genetically modified cascade components. Our modelling approach recapitulates a number of recent findings in vertebrate phototransduction. First, our results are in line with the recently established requirement of dimeric activation of PDE6 by transducin and further show that such conditions can be fulfilled at the expense of a significant excess of G protein activated by rhodopsin. Secondly, simulations suggest a crucial role of the recoverin-mediated Ca2+-feedback on rhodopsin kinase in accelerating the shutoff, when light flashes are delivered in the presence of a light background. Finally, stochastic simulations suggest that transient complexes between dark rhodopsin and transducin formed prior to light stimulation increase the reproducibility of single photon responses. Current limitations of the model are likely associated with the yet unknown mechanisms governing the shutoff of the cascade. |
| Databáze: | OpenAIRE |
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