| First Author | Baruch A | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 31 | Pages | 28999-9006 |
| PubMed ID | 11395508 | Mgi Jnum | J:120518 |
| Mgi Id | MGI:3706721 | Doi | 10.1074/jbc.M103628200 |
| Citation | Baruch A, et al. (2001) Defining a link between gap junction communication, proteolysis, and cataract formation. J Biol Chem 276(31):28999-9006 |
| abstractText | Disruption of the connexin alpha 3 (Cx46) gene (alpha 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 gamma-crystallin, leading to its aggregation and subsequent opacification of the lens. The general cysteine protease inhibitor, E-64, blocked cataract formation and gamma-crystallin cleavage in alpha 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 alpha 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 alpha 3 (-/-) lenses. These data establish a role for alpha 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. |
