Cancer Institute A national cancer institute
designated cancer center

Matthew Bogyo

Publication Details

  • Defining a link between gap junction communication, proteolysis, and cataract formation JOURNAL OF BIOLOGICAL CHEMISTRY Baruch, A., Greenbaum, D., Levy, E. T., Nielsen, P. A., GILULA, N. B., KUMAR, N. M., Bogyo, M. 2001; 276 (31): 28999-29006

    Abstract:

    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.

    View details for Web of Science ID 000170346000050

    View details for PubMedID 11395508

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