MOLECULAR BIOLOGY, STRUCTURES AND FUNCTION OF CRYSTALLINS

点击翻译按钮获取中文摘要

The normal lens depends on abundant proteins known as crystallins for its clarity. Crystallins are multifunctional proteins, recruited to the lens but often retaining other functions important in non-lens tissues. One example we have discovered is mu-crystallin which is not only a major lens protein in some mammals but is also expressed abundantly in retina where it may serve as an enzyme of amino acid metabolism with importance for photoreceptors. We have cloned and mapped the human gene for mu-crystallin and are examining its expression in retina and lens. Another major group of lens proteins, the gamma-crystallins were thought to be highly specific for lens, but we have found that gammas-crystallin is also expressed in retina. We have cloned and mapped the mouse gammas gene and shown it to be the locus for Opj, a genetic cataract in mice. We have synthesized normal and Opj mutant gammas proteins to study the basis of the cataract. We have also synthesized proteins for structural analysis of AIM1, a melanoma-associated protein related to gamma-crystallin. We have characterized the gene promoter of zeta-crystallin and have shown that a specific form of Pax6 is essential for its function. A second factor, Nrl, is required for high level expression and a third element, designated BPE, is necessary to suppress "collateral" expression in brain. Macrophage migration inhibitory factor (MIF) is a delayed early response gene expressed in lens, retina, cornea and elsewhere. We have cloned and mapped human and mouse genes for MIF and the related D-dopachrome tautomerase. We have synthesized recombinant proteins to study MIF activity in suppression of NK T-cell cytotoxicity in aqueous humor, the possible enzymatic role of MIF and the structure of MIF in solution. A collaborative "gene knockout" experiment for MIF is also in progress.