Abstract

We propose to investigate the cellular organization of the mammalian lens and its possible relation to cataract by determining the three-dimensional structure of the fiber gap junctions. Up to 60% of the lens fiber surface is composed of junctions that are thought to belong to the communicating type. This unique cellular arrangement will allow the study of cell communication at the molecular level. We will investigate the junctions in isolation by electron microscopy and X-ray diffraction methods to determine three basic characteristics of the functional units (connexons): a) the oligomeric arrangement of the connexons, b) the secondary structure of the connexon subunit; and c) the conformational changes that the connexons must undergo to mediate and regulate permeability. In addition, by reconstituting the connexons into unilamellar liposomes, we shall measure the permeability changes in vitro to test directly the hypothesis that connexons are the units mediating and regulating permeability.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004110-05
Application #
3258582
Study Section
Biophysics and Biophysical Chemistry B Study Section (BBCB)
Project Start
1982-08-01
Project End
1988-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Zampighi, Guido A; Serrano, Raul; Vergara, Julio L (2014) A novel synaptic vesicle fusion path in the rat cerebral cortex: the ""saddle"" point hypothesis. PLoS One 9:e100710
Souda, Puneet; Ryan, Christopher M; Cramer, William A et al. (2011) Profiling of integral membrane proteins and their post translational modifications using high-resolution mass spectrometry. Methods 55:330-6
Schietroma, C; Fain, N; Zampighi, L M et al. (2009) The structure of the cytoplasm of lens fibers as determined by conical tomography. Exp Eye Res 88:566-74
Salvi, Eleonora; Cantele, Francesca; Zampighi, Lorenzo et al. (2008) JUST (Java User Segmentation Tool) for semi-automatic segmentation of tomographic maps. J Struct Biol 161:287-97
Zampighi, Guido A; Fain, Nick; Zampighi, Lorenzo M et al. (2008) Conical electron tomography of a chemical synapse: polyhedral cages dock vesicles to the active zone. J Neurosci 28:4151-60
Cantele, Francesca; Zampighi, Lorenzo; Radermacher, Michael et al. (2007) Local refinement: an attempt to correct for shrinkage and distortion in electron tomography. J Struct Biol 158:59-70
Zampighi, G A; Zampighi, L M; Fain, N et al. (2006) Conical electron tomography of a chemical synapse: vesicles docked to the active zone are hemi-fused. Biophys J 91:2910-8
Lin, Dingbo; Barnett, Micheal; Lobell, Samuel et al. (2006) PKCgamma knockout mouse lenses are more susceptible to oxidative stress damage. J Exp Biol 209:4371-8
Hegde, Balachandra G; Isas, J Mario; Zampighi, Guido et al. (2006) A novel calcium-independent peripheral membrane-bound form of annexin B12. Biochemistry 45:934-42
Zampighi, Guido A; Kreman, Michael; Lanzavecchia, Salvatore et al. (2003) Structure of functional single AQP0 channels in phospholipid membranes. J Mol Biol 325:201-10

Showing the most recent 10 out of 38 publications