The absorption of photons in rods and cones of the retina activates a cascade of biochemical reactions (phototransduction cascade) that generates the electrical response to light. The activation and deactivation of the cascade ultimately limits the amplitude and kinetics of the transduced signal, and thus the sensitivity and temporal resolution of vision. The overall goal of this study is to understand the mechanisms that turn off the light response in intact mouse photoreceptors. Gene targeting techniques will be used to manipulate the function of a subset of proteins that have been suggested to play key roles in deactivation of the cascade, and the resulting changes in the photo responses of single rod cells will be determined by electrical recording. Using this approach, we will ask: (1) What are the mechanisms that produce the timely and reproducible deactivation of rhodopsin? (2) What protein interactions facilitate transducin and PDE deactivation in intact cells, and does this deactivation normally rate-limit response recovery? and (3) What deactivation step(s) are speeded during light adaptation? This research will help clarify the initial steps in the normal visual process, as well as the pathogenesis of diseases that arise from failures of deactivation, such as in some forms of retinitis pigmentosa and Oguchi disease. More generally, these experiments will provide insights into the mechanisms of deactivation of G protein cascades, which all cell types use to transduce extracellular signals into intracellular responses.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY014047-04
Application #
6888064
Study Section
Special Emphasis Panel (ZRG1-VISC (02))
Program Officer
Mariani, Andrew P
Project Start
2002-05-01
Project End
2006-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
4
Fiscal Year
2005
Total Cost
$294,567
Indirect Cost
Name
University of California Davis
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
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Peinado Allina, Gabriel; Fortenbach, Christopher; Naarendorp, Franklin et al. (2017) Bright flash response recovery of mammalian rods in vivo is rate limited by RGS9. J Gen Physiol 149:443-454
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Fortenbach, Christopher R; Kessler, Christopher; Peinado Allina, Gabriel et al. (2015) Speeding rod recovery improves temporal resolution in the retina. Vision Res 110:57-67
Gross, Owen P; Pugh Jr, Edward N; Burns, Marie E (2015) cGMP in mouse rods: the spatiotemporal dynamics underlying single photon responses. Front Mol Neurosci 8:6
Zhang, Pengfei; Goswami, Mayank; Zam, Azhar et al. (2015) Effect of scanning beam size on the lateral resolution of mouse retinal imaging with SLO. Opt Lett 40:5830-3
Kessler, Christopher; Tillman, Megan; Burns, Marie E et al. (2014) Rhodopsin in the rod surface membrane regenerates more rapidly than bulk rhodopsin in the disc membranes in vivo. J Physiol 592:2785-97
Levine, Emily S; Zam, Azhar; Zhang, Pengfei et al. (2014) Rapid light-induced activation of retinal microglia in mice lacking Arrestin-1. Vision Res 102:71-9
Arshavsky, Vadim Y; Burns, Marie E (2014) Current understanding of signal amplification in phototransduction. Cell Logist 4:e29390

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