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Network-level analysis of light adaptation in rod cells under normal and altered conditions

Dell'Orco, Daniele LU ; Schmidt, Henning; Mariani, Simona and Fanelli, Francesca (2009) In Molecular BioSystems 5(10). p.1232-1246
Abstract
Photoreceptor cells finely adjust their sensitivity and electrical response according to changes in light stimuli as a direct consequence of the feedback and regulation mechanisms in the phototransduction cascade. In this study, we employed a systems biology approach to develop a dynamic model of vertebrate rod phototransduction that accounts for the details of the underlying biochemistry. Following a bottom-up strategy, we first reproduced the results of a robust model developed by Hamer et al. (Vis. Neurosci., 2005, 22(4), 417), and then added a number of additional cascade reactions including: (a) explicit reactions to simulate the interaction between the activated effector and the regulator of G-protein signalling (RGS); (b) a reaction... (More)
Photoreceptor cells finely adjust their sensitivity and electrical response according to changes in light stimuli as a direct consequence of the feedback and regulation mechanisms in the phototransduction cascade. In this study, we employed a systems biology approach to develop a dynamic model of vertebrate rod phototransduction that accounts for the details of the underlying biochemistry. Following a bottom-up strategy, we first reproduced the results of a robust model developed by Hamer et al. (Vis. Neurosci., 2005, 22(4), 417), and then added a number of additional cascade reactions including: (a) explicit reactions to simulate the interaction between the activated effector and the regulator of G-protein signalling (RGS); (b) a reaction for the reformation of the G-protein from separate subunits; (c) a reaction for rhodopsin (R) reconstitution from the association of the opsin apoprotein with the 11-cis-retinal chromophore; (d) reactions for the slow activation of the cascade by opsin. The extended network structure successfully reproduced a number of experimental conditions that were inaccessible to prior models. With a single set of parameters the model was able to predict qualitative and quantitative features of rod photoresponses to light stimuli ranging over five orders of magnitude, in normal and altered conditions, including genetic manipulations of the cascade components. In particular, the model reproduced the salient dynamic features of the rod from Rpe65(-/-) animals, a well established model for Leber congenital amaurosis and vitamin A deficiency. The results of this study suggest that a systems-level approach can help to unravel the adaptation mechanisms in normal and in disease-associated conditions on a molecular basis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular BioSystems
volume
5
issue
10
pages
1232 - 1246
publisher
Royal Society of Chemistry
external identifiers
  • wos:000269835400016
  • scopus:70349339354
ISSN
1742-2051
DOI
10.1039/b908123b
language
English
LU publication?
yes
id
e5525a34-aaf1-4c93-881a-2c67536c98c2 (old id 1490646)
date added to LUP
2009-10-19 13:33:45
date last changed
2017-12-10 04:23:17
@article{e5525a34-aaf1-4c93-881a-2c67536c98c2,
  abstract     = {Photoreceptor cells finely adjust their sensitivity and electrical response according to changes in light stimuli as a direct consequence of the feedback and regulation mechanisms in the phototransduction cascade. In this study, we employed a systems biology approach to develop a dynamic model of vertebrate rod phototransduction that accounts for the details of the underlying biochemistry. Following a bottom-up strategy, we first reproduced the results of a robust model developed by Hamer et al. (Vis. Neurosci., 2005, 22(4), 417), and then added a number of additional cascade reactions including: (a) explicit reactions to simulate the interaction between the activated effector and the regulator of G-protein signalling (RGS); (b) a reaction for the reformation of the G-protein from separate subunits; (c) a reaction for rhodopsin (R) reconstitution from the association of the opsin apoprotein with the 11-cis-retinal chromophore; (d) reactions for the slow activation of the cascade by opsin. The extended network structure successfully reproduced a number of experimental conditions that were inaccessible to prior models. With a single set of parameters the model was able to predict qualitative and quantitative features of rod photoresponses to light stimuli ranging over five orders of magnitude, in normal and altered conditions, including genetic manipulations of the cascade components. In particular, the model reproduced the salient dynamic features of the rod from Rpe65(-/-) animals, a well established model for Leber congenital amaurosis and vitamin A deficiency. The results of this study suggest that a systems-level approach can help to unravel the adaptation mechanisms in normal and in disease-associated conditions on a molecular basis.},
  author       = {Dell'Orco, Daniele and Schmidt, Henning and Mariani, Simona and Fanelli, Francesca},
  issn         = {1742-2051},
  language     = {eng},
  number       = {10},
  pages        = {1232--1246},
  publisher    = {Royal Society of Chemistry},
  series       = {Molecular BioSystems},
  title        = {Network-level analysis of light adaptation in rod cells under normal and altered conditions},
  url          = {http://dx.doi.org/10.1039/b908123b},
  volume       = {5},
  year         = {2009},
}