The purpose of the proposed study is to determine if CaBP5 is crucial for vision. The long-term goal is to determine the physiological function of CaBP5 in the retina. CaBP5 is a member of a subfamily of neuronal calcium-binding proteins with similarity to calmodulin. CaBPs have been shown to modulate in vitro various targets known to also be regulated by calmodulin including voltage-dependent calcium-channels. The crucial role of CaBP4 for both rod and cone visual function suggests that CaBPs are an important family of proteins that are required for vision. CaBP5 is expressed in a subset of retina bipolar cells. Bipolar cells are interneurons that transmit the visual signal from photoreceptors to ganglion cells and/or amacrine cells and are critical for our vision. The current application will focus on the characterization of a knockout mouse model in which CaBP5 is deleted. Our hypothesis is that CaBP5 shares the same functional role with other CaBPs but in a specific cell type and can modulate voltage-dependent Ca2+ channels. To understand the role of CaBP5 in bipolar cell signaling, we propose 1) to determine the retinal proteins that interact with CaBP5 with in vitro biochemical approaches and in vivo screenings of a retina cDNA library using the two-hybrid system, 2) to characterize CaBP5 knockout mice;patch clamp recordings and ERG experiments will allow us to determine if the role of CaBP5 is crucial for our vision and the effect of CaBP5 deletion on the retina structure will also be analyzed using microscopy;and 3) to determine if CaBP5 interacts with and modulates voltage-dependent calcium channels, targets known to be modulated by CaBP1 and CaBP4.

Public Health Relevance

Neuronal Ca2+-binding proteins are directly involved in ocular pathologies. For example, mutations in the Cabp4 gene, a member of the subfamily of CaBPs investigated in this application, have been associated with congenital stationary night blindness. Therefore, elucidating the function of Ca2+-binding proteins in the retina will not only contribute to our understanding of the basic processes of vision, but will also allow us to better understand eye pathologies. The proposed study will give insight into the role of CaBP5 in the retina and will determine if this calcium-binding protein is crucial for our vision. Identifying the role of CaBP5 will not only contribute to our understanding of the basic processes modulated by CaBP5, but might give insight into the contribution of a specific subset of bipolar cells that express CaBP5 in visual processing.

National Institute of Health (NIH)
National Eye Institute (NEI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-CB-G (90))
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Greenwell, Thomas
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University of Washington
Schools of Medicine
United States
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Sokal, Izabela; Haeseleer, Francoise (2011) Insight into the role of Ca2+-binding protein 5 in vesicle exocytosis. Invest Ophthalmol Vis Sci 52:9131-41
Rieke, Fred; Lee, Amy; Haeseleer, Francoise (2008) Characterization of Ca2+-binding protein 5 knockout mouse retina. Invest Ophthalmol Vis Sci 49:5126-35