|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 31, 28999-29006, August 3, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Disruption of the connexin
Defining a Link between Gap Junction Communication,
Proteolysis, and Cataract Formation*
§,,
Department of Biochemistry and Biophysics,
University of California, San Francisco, California 94143 and the
§ Department of Cell Biology, Scripps Research Institute,
La Jolla, California 92037
3
(Cx46) gene (3 (
/)) in mice results in severe cataracts within
the nuclear portion of the lens. These cataracts are associated with
proteolytic processing of the abundant lens protein 
-crystallin,
leading to its aggregation and subsequent opacification of the lens.
The general cysteine protease inhibitor, E-64, blocked cataract
formation and -crystallin cleavage in 3 (/) lenses. Using a
new class of activity-based cysteine protease affinity probes, we
identified the calcium-dependent proteases, m-calpain and
Lp82, as the primary targets of E-64 in the lens. Profiling changes in
protease activities throughout cataractogenesis indicated that Lp82
activity was dramatically increased in 3 (/) lenses and
correlated both spatially and temporally with cataract formation.
Increased Lp82 activity was due to calcium accumulation as a result of
increased influx and decreased outflux of calcium ions in 3 (/)
lenses. These data establish a role for 3 gap junctions in
maintaining calcium homeostasis that in turn is required to control
activity of the calcium-dependent cysteine protease Lp82,
shown here to be a key initiator of the process of cataractogenesis.
*
This work was supported by National Institutes of Health
Grants GM37904 and Ey12142 (to A. B., N. B. G., and
N. M. K.) and by funding from the Sandler Program in Basic
Sciences (to M. B. and D. G.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence may be addressed: Campus Box 0448, Dept. of Biochemistry and Biophysics, University of California, San
Francisco, 513 Parnassus Ave., San Francisco, CA 94122. Tel.: 415-502-8142; E-mail: mbogyo@biochem.ucsf.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Bornheim, M. Muller, U. Reuter, H. Herrmann, H. Bussow, and T. M. Magin A dominant vimentin mutant upregulates Hsp70 and the activity of the ubiquitin-proteasome system, and causes posterior cataracts in transgenic mice J. Cell Sci., November 15, 2008; 121(22): 3737 - 3746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fujimoto, K. Oshima, T. Shinkawa, B. B. Wang, S. Inouye, N. Hayashida, R. Takii, and A. Nakai Analysis of HSF4 Binding Regions Reveals Its Necessity for Gene Regulation during Development and Heat Shock Response in Mouse Lenses J. Biol. Chem., October 31, 2008; 283(44): 29961 - 29970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Li, B. Chang, C. Cheng, D. Chang, N. L. Hawes, C.-h. Xia, and X. Gong Dense Nuclear Cataract Caused by the {gamma}B-Crystallin S11R Point Mutation Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 304 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tang, X. Liu, R. K. Zoltoski, L. A. Novak, R. A. Herrera, I. Richard, J. R. Kuszak, and N. M. Kumar Age-Related Cataracts in {alpha}3Cx46-Knockout Mice Are Dependent on a Calpain 3 Isoform Invest. Ophthalmol. Vis. Sci., June 1, 2007; 48(6): 2685 - 2694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Canas, D. Lopez-Ferrer, A. Ramos-Fernandez, E. Camafeita, and E. Calvo Mass spectrometry technologies for proteomics Brief Funct Genomic Proteomic, February 1, 2006; 4(4): 295 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. P. Udupa and K. K. Sharma Effect of Oxidized {beta}B3-Crystallin Peptide on Lens {beta}L-Crystallin: Interaction with {beta}B2-Crystallin Invest. Ophthalmol. Vis. Sci., July 1, 2005; 46(7): 2514 - 2521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Martinez-Wittinghan, C. Sellitto, T. W. White, R. T. Mathias, D. Paul, and D. A. Goodenough Lens Gap Junctional Coupling Is Modulated by Connexin Identity and the Locus of Gene Expression Invest. Ophthalmol. Vis. Sci., October 1, 2004; 45(10): 3629 - 3637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gao, X. Sun, F. J. Martinez-Wittinghan, X. Gong, T. W. White, and R. T. Mathias Connections Between Connexins, Calcium, and Cataracts in the Lens J. Gen. Physiol., September 27, 2004; 124(4): 289 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Chaerkady and K. K. Sharma Characterization of a Bradykinin-Hydrolyzing Protease from the Bovine Lens Invest. Ophthalmol. Vis. Sci., April 1, 2004; 45(4): 1214 - 1223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Lurtz and C. F. Louis Calmodulin and protein kinase C regulate gap junctional coupling in lens epithelial cells Am J Physiol Cell Physiol, December 1, 2003; 285(6): C1475 - C1482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Gerido, C. Sellitto, L. Li, and T. W. White Genetic Background Influences Cataractogenesis, but Not Lens Growth Deficiency, in Cx50-Knockout Mice Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2669 - 2674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Nielsen, A. Baruch, V. I. Shestopalov, B. N.G. Giepmans, I. Dunia, E. L. Benedetti, and N. M. Kumar Lens Connexins {alpha}3Cx46 and {alpha}8Cx50 Interact with Zonula Occludens Protein-1 (ZO-1) Mol. Biol. Cell, June 1, 2003; 14(6): 2470 - 2481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lin, D. L. Boyle, and D. J. Takemoto IGF-I-Induced Phosphorylation of Connexin 43 by PKC{gamma}: Regulation of Gap Junctions in Rabbit Lens Epithelial Cells Invest. Ophthalmol. Vis. Sci., March 1, 2003; 44(3): 1160 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Adam, E. J. Sorensen, and B. F. Cravatt Chemical Strategies for Functional Proteomics Mol. Cell. Proteomics, October 1, 2002; 1(10): 781 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Greenbaum, A. Baruch, L. Hayrapetian, Z. Darula, A. Burlingame, K. F. Medzihradszky, and M. Bogyo Chemical Approaches for Functionally Probing the Proteome Mol. Cell. Proteomics, January 1, 2002; 1(1): 60 - 68. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |