This study reports the first demonstration of a marked reduction in α- crystallin chaperone activity in an experimental model of cataract, and the study implicates activation of the cysteine protease calpain II (EC 126.96.36.199) as the in vivo protease responsible for decreased chaperone activity. Chaperone activity of normal α-crystallin from lenses of young rats was assayed by measuring attenuation of heat-induced aggregation and scattering of βL-crystallin. α-Crystallin from the nucleus of lenses with selenite cataract showed specific selective proteolysis, and chaperone activity was diminished. Proteolysis of α-crystallin from selenite cataract lenses was mimicked by incubating normal α-crystallin with calpain II, and this also resulted in loss of chaperone activity. Two-dimensional gel electrophoresis and peptide mapping were used to identify four partially degraded αA- and αB-crystallin polypeptides following incubation of normal α-crystallin with calpain. Similar partially degraded αA- and αB polypeptides were found in selenite cataract. Previous experiments indicated that α-crystallin chaperone activity decreases because of removal of the COOH terminus. Our experiments support this observation and suggest that calpain proteolysis of α-crystallin at the COOH terminus may result in a loss of chaperone activity in selenite cataract.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Biological Chemistry|
|State||Published - Jan 1 1993|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology