Retinal rods utilize a prototypical G-protein signaling cascade to encode our visual scene under dim light. Often, defects in the molecular components of this cascade, or their over-stimulation by bright light, cause blinding disorders in humans.
The first aim will investigate biochemical cascades in rods following bright light exposure that may slow dark adaptation.
The second aim i s to investigate the induction of endoplasmic stress by bright light exposure and mis-folded rhodopsin with the goal towards manipulation of these pathways to prolong photoreceptor cell survival. The long term objective of this proposal is to understand phototransduction in normal function and dysfunction so that this knowledge can be used to devise strategies for the treatment of human visual disorders.

Public Health Relevance

Photoreceptor cells utilize a prototypical G-protein signaling cascade to convey the presence of light. Genetic mutations and environmental factors that affect the performance of this signaling cascade cause many different forms of blinding diseases through mechanisms that are not well defined. A thorough understanding of these mechanisms will help in the design of treatment options.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY012155-15
Application #
8296223
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Neuhold, Lisa
Project Start
1998-03-01
Project End
2015-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
15
Fiscal Year
2012
Total Cost
$602,705
Indirect Cost
$234,828
Name
University of Southern California
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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Berry, Justin; Frederiksen, Rikard; Yao, Yun et al. (2016) Effect of Rhodopsin Phosphorylation on Dark Adaptation in Mouse Rods. J Neurosci 36:6973-87
Sakurai, Keisuke; Chen, Jeannie; Khani, Shahrokh C et al. (2015) Regulation of mammalian cone phototransduction by recoverin and rhodopsin kinase. J Biol Chem 290:9239-50
Vinberg, Frans; Wang, Tian; Molday, Robert S et al. (2015) A new mouse model for stationary night blindness with mutant Slc24a1 explains the pathophysiology of the associated human disease. Hum Mol Genet 24:5915-29
Azevedo, Anthony W; Doan, Thuy; Moaven, Hormoz et al. (2015) C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor. Elife 4:
Wang, Tian; Chen, Jeannie (2014) Induction of the unfolded protein response by constitutive G-protein signaling in rod photoreceptor cells. J Biol Chem 289:29310-21
Hoyo, Natalia López-Del; López-Begines, Santiago; Rosa, Jose Luis et al. (2014) Functional EF-hands in neuronal calcium sensor GCAP2 determine its phosphorylation state and subcellular distribution in vivo, and are essential for photoreceptor cell integrity. PLoS Genet 10:e1004480
Moaven, Hormoz; Koike, Yukihiro; Jao, Christine C et al. (2013) Visual arrestin interaction with clathrin adaptor AP-2 regulates photoreceptor survival in the vertebrate retina. Proc Natl Acad Sci U S A 110:9463-8
Mao, Wen; Miyagishima, K J; Yao, Yun et al. (2013) Functional comparison of rod and cone Gα(t) on the regulation of light sensitivity. J Biol Chem 288:5257-67
Song, Xiufeng; Seo, Jungwon; Baameur, Faiza et al. (2013) Rapid degeneration of rod photoreceptors expressing self-association-deficient arrestin-1 mutant. Cell Signal 25:2613-24

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