A comparative view of alpha crystallins: The contribution of comparative studies to understanding function

Abstract

Integration between comparative biology and cellular/molecular biology has helped advance understanding of the structure, function and physiology of the vertebrate small heat shock proteins αA- and αB-crystallin. These proteins are expressed at high concentration in the eye lens where they contribute to transparency and refractive power. But they also function similarly to molecular chaperones by preventing the aggregation of denatured proteins that can cause opacities, or cataracts. α-crystallins also serve a number of other roles in and out of the lens that are still not completely understood. Comparative examination of α-crystallins and closely related small heat shock proteins from diverse taxa has helped provide insights into the proteins' three-dimensional shape and structure/function relationships. Until recently, no studies had examined the tissue specific expression or chaperone-like activity of α-crystallins from a non-mammalian vertebrate. I have been investigating the α-crystallins of the zebrafish, Danio rerio, as a first step towards utilizing the bony fishes as a model group for understanding the evolution of α-crystallin function. Zebrafish αA-crystallin displays similar structure and expression and increased chaperone-like activity compared to its human orthologue. Zebrafish αB-crystallin, however, has a truncated C-terminal extension, more limited expression and lower chaperone-like activity than its human orthologue. These data suggest that αA-crystallin physiological function may be conserved between zebrafish and mammals, while αB-crystallin physiological function has diverged. Understanding zebrafish α-crystallin physiology is necessary before this species can be used for developmental and genetic studies, and provides a foundation for further comparative studies.