A Comparative View of Alpha Crystallins: The contribution of comparative studies to understanding function

Integration between comparative biology and cellular/molecularbiology has helped advance understanding of the structure, functionand physiology of the vertebrate small heat shock proteins A-and B-crystallin. These proteins are expressed at high concentrationin the eye lens where they contribute to transparency and refractivepower. But they also function similarly to molecular chaperonesby preventing the aggregation of denatured proteins that cancause opacities, or cataracts. -crystallins also serve a numberof other roles in and out of the lens that are still not completelyunderstood. Comparative examination of -crystallins and closelyrelated small heat shock proteins from diverse taxa has helpedprovide insights into the proteins' three-dimensional shapeand structure/function relationships. Until recently, no studieshad examined the tissue specific expression or chaperone-likeactivity of -crystallins from a non-mammalian vertebrate. Ihave been investigating the -crystallins of the zebrafish, Daniorerio, as a first step towards utilizing the bony fishes asa model group for understanding the evolution of -crystallinfunction. Zebrafish A-crystallin displays similar structureand expression and increased chaperone-like activity comparedto its human orthologue. Zebrafish B-crystallin, however, hasa truncated C-terminal extension, more limited expression andlower chaperone-like activity than its human orthologue. Thesedata suggest that A-crystallin physiological function may beconserved between zebrafish and mammals, while B-crystallinphysiological function has diverged. Understanding zebrafish-crystallin physiology is necessary before this species canbe used for developmental and genetic studies, and providesa foundation for further comparative studies.