A hybrid stochastic/deterministic model of single photon response and light adaptation in mouse rods.
ADP, adenosine diphosphate
ATP, adenosine-5′-triphosphate
Arr, arrestin
BG, background illumination
CNG, cyclic nucleotide-gated (channel)
CSM, completely substituted mutant of rhodopsin
CV, coefficient of variation
DM, deterministic model
Dynamic modeling
E, effector of the phototransduction cascade, activated PDE
FFT, fast Fourier-transform
GC, guanylate cyclase
GCAPs, guanylate cyclase-activating proteins
GDP, guanosine-5′-diphosphate
GPCR, G protein-coupled receptor
GTP, guanosine-5′-triphosphate
Gt, G protein/transducin
Gα, α-subunit of the G protein
Gβγ, β- and γ-subunit of the G protein
HSDM, hybrid stochastic/deterministic model
Light adaptation
MPR, multiple photon response
PDE, phosphodiesterase 6
Ph, photons
Phototransduction
R, rhodopsin
RGS, regulator of G protein signaling
RK, rhodopsin kinase
ROS, rod outer segment
Rec, recoverin
Rn, activated rhodopsin that has been phosphorylated n times
SD, standard deviation
SPR, single photon response
Stochastic simulation
Systems biology
TTP, time to peak
cGMP, cyclic guanosine monophosphate
ΔJ, photocurrent
ΔU, photovoltage
Journal
Computational and structural biotechnology journal
ISSN: 2001-0370
Titre abrégé: Comput Struct Biotechnol J
Pays: Netherlands
ID NLM: 101585369
Informations de publication
Date de publication:
2021
2021
Historique:
received:
04
04
2021
revised:
19
06
2021
accepted:
21
06
2021
entrez:
21
7
2021
pubmed:
22
7
2021
medline:
22
7
2021
Statut:
epublish
Résumé
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 Ca
Identifiants
pubmed: 34285774
doi: 10.1016/j.csbj.2021.06.033
pii: S2001-0370(21)00271-3
pmc: PMC8258797
doi:
Types de publication
Journal Article
Langues
eng
Pagination
3720-3734Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
Biochim Biophys Acta. 2015 Jan;1848(1 Pt A):26-34
pubmed: 25305340
Biochemistry. 2005 Nov 15;44(45):14695-700
pubmed: 16274216
Biochem Soc Trans. 2010 Oct;38(5):1275-80
pubmed: 20863298
J Gen Physiol. 2003 Oct;122(4):419-44
pubmed: 12975449
J Gen Physiol. 2021 Feb 1;153(2):
pubmed: 33502442
Nature. 1997 Oct 2;389(6650):505-9
pubmed: 9333241
Biochem Biophys Res Commun. 2015 Jun 12;461(4):665-70
pubmed: 25918020
PLoS One. 2020 Feb 7;15(2):e0226123
pubmed: 32032370
FEBS Lett. 2013 Jan 4;587(1):1-4
pubmed: 23178927
Vis Neurosci. 2005 Jul-Aug;22(4):417-36
pubmed: 16212700
J Neurophysiol. 1996 Aug;76(2):698-714
pubmed: 8871192
Proc Natl Acad Sci U S A. 2019 Mar 12;116(11):5144-5153
pubmed: 30796193
Mol Biosyst. 2009 Oct;5(10):1232-46
pubmed: 19756313
HardwareX. 2020 Oct;8:e00155
pubmed: 33615085
Biophys J. 1998 Feb;74(2 Pt 1):831-42
pubmed: 9533695
Structure. 2015 Apr 7;23(4):628-38
pubmed: 25728926
Open Biol. 2021 Jan;11(1):200346
pubmed: 33401992
J Physiol. 2012 Aug 15;590(16):3841-55
pubmed: 22641773
Open Biol. 2020 Jan;10(1):190241
pubmed: 31910741
Biophys J. 2015 Feb 3;108(3):778-9
pubmed: 25650945
Neuron. 2020 Jul 22;107(2):320-337.e6
pubmed: 32473094
Elife. 2014;3:e01386
pubmed: 24399457
Commun Biol. 2019 Jun 14;2:209
pubmed: 31240247
Open Biol. 2018 Aug;8(8):
pubmed: 30068566
J Physiol. 2020 Sep;598(17):3747-3763
pubmed: 32557629
Curr Biol. 2014 Dec 15;24(24):2888-98
pubmed: 25454583
Front Mol Neurosci. 2015 Nov 17;8:67
pubmed: 26635520
PLoS One. 2007 Dec 19;2(12):e1327
pubmed: 18091997
Neuron. 2000 Oct;28(1):153-64
pubmed: 11086991
FEBS Lett. 2013 Jun 27;587(13):2060-6
pubmed: 23684654
Mol Biosyst. 2014 Jun;10(6):1481-9
pubmed: 24675755
Syst Biol (Stevenage). 2006 Mar;153(2):53-60
pubmed: 16986253
Cell Calcium. 2017 Jul;65:40-51
pubmed: 28238353
Biophys J. 2014 Sep 2;107(5):1042-1053
pubmed: 25185540
J Neurosci Methods. 2006 Jun 30;154(1-2):1-18
pubmed: 16554092
Cell Commun Signal. 2013 May 21;11(1):36
pubmed: 23693153
Open Biol. 2018 Aug;8(8):
pubmed: 30068567
Biophys J. 2015 Feb 3;108(3):775-7
pubmed: 25650944
Biochemistry. 1997 Jul 29;36(30):9253-60
pubmed: 9230059
Proc Natl Acad Sci U S A. 2019 Apr 30;116(18):8653-8654
pubmed: 31040258
Wiley Interdiscip Rev Syst Biol Med. 2010 Jul-Aug;2(4):385-397
pubmed: 20836037
Neuron. 2002 May 30;34(5):773-85
pubmed: 12062023
Neuron. 2002 Sep 26;36(1):81-91
pubmed: 12367508
Biochem J. 2011 Dec 1;440(2):263-71
pubmed: 21843151
FEBS Lett. 2007 Mar 6;581(5):944-8
pubmed: 17300784
FEBS Lett. 2008 Mar 19;582(6):991-6
pubmed: 18307992
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3718-22
pubmed: 10097103
J Physiol. 2015 Jul 1;593(13):2975-6
pubmed: 26123098
Nat Commun. 2017 Nov 27;8(1):1813
pubmed: 29180667
PLoS One. 2012;7(1):e29812
pubmed: 22279546
ACS Chem Neurosci. 2013 Jun 19;4(6):909-17
pubmed: 23472635
J Physiol. 1986 Feb;371:115-45
pubmed: 2422346
Sci Rep. 2019 Dec 27;9(1):20105
pubmed: 31882816