POSNER, M.; HORWITZ, J.; Ashland University; Univ. of California, Los Angeles: A Comparative View of Alpha Crystallin Chaperone Function in the Vertebrate Lens
The small heat shock protein (sHSP) alpha crystallin contributes greatly to the refractive index of the vertebrate eye lens. Like other sHSP, both the alpha A and alpha B subunits also act as molecular chaperones by preventing the aggregation of denatured proteins. It has been hypothesized that this chaperone function helps prevent age-related opacities, or cataracts, in the mammalian lens. Lack of studies on alpha crystallin chaperone function in non-mammalian vertebrates makes it difficult to determine the ancestral role of this protein in the vertebrate lens. We used molecular techniques to produce recombinant alpha crystallins from the zebrafish and assayed their ability to prevent the aggregation of denatured proteins. Both subunits exhibited chaperone function, with alpha A providing greater protection than alpha B near zebrafish physiological temperature (30° C). At 37° C zebrafish alpha A crystallin exhibited chaperone function comparable to its human orthologue. These data may reflect an evolutionary change in the relative protective role of these two alpha crystallin subunits in the vertebrate lens. In another study we are using the closely related sHsp 16.5 from the hyperthermophilic bacterium Methanococcus janaschii to help elucidate the quaternary structure and the mechanism behind alpha crystallin chaperone function. These and future comparative studies can provide insights into the role of alpha crystallin in the mammalian lens not available by studying only mammalian systems. A broader comparative examination of alpha crystallin function can also help detail how and why a heat shock protein became co-opted to play an important role in vertebrate vision.
