The long-term goal of this project is to understand the physiological role of the major intrinsic protein of the lens of the eye. This protein, called MIP 26, has been sequenced from its cDNA-clone, and has a molecular weight of 28.2kD. It is thought to be a major structural feature of lens fiber junctions, and may be the connexon channel itself. Antibodies to MIP 26 have been shown to block transfer of dye between cultured lens-fiber cells. Changes in MIP 26 are associated with cataract formation. We have reconstituted MIP 26 into planar bilayers and shown that it produces voltage-dependent channels blocked by an antibody to MIP 26. Moreover we have been able to alter the functional characteristics of the channels using Ca++-calmodulin and proteolytic digestion. We propose to use planar bilayer methods study the reconstituted channel. In particular we will examine biochemical modifications of the channel and block of the channel by various well- characterized antibodies. We hope these studies will tell us how many molecules of MIP 26 form a single channel and suggest possible physiological roles for the channel. We will also pursue electrophysiological studies of a chick-lens system which very likely expresses channels due to MIP. We hope to be able to make a direct comparison between MIP channels in bilayers and those in this culture system. We hope this direct comparison will elucidate the function of MIP 26 in the lens.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005661-08
Application #
3260977
Study Section
Special Emphasis Panel (SSS (01))
Project Start
1985-03-01
Project End
1993-06-30
Budget Start
1992-03-01
Budget End
1993-06-30
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
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Clemens, Daniel M; Németh-Cahalan, Karin L; Trinh, Lien et al. (2013) In vivo analysis of aquaporin 0 function in zebrafish: permeability regulation is required for lens transparency. Invest Ophthalmol Vis Sci 54:5136-43
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