dipalmitoylphosphatidylserine and Cataract

Vertebrate lens is one of the tissues with the highest soluble protein concentration. The predominant soluble proteins in lens fiber cells are crystallins, and among them, α-crystallins belong to the small heat shock protein family with chaperone-like activity. Although α-crystallins are highly soluble in waters, α-crystallins have been detected in the membrane-bound fraction of lens, which will increase in the aged or cataractous lens. In this research, we found αA-crystallin exhibited a complex thermal transition with remarkable changes in secondary and quaternary structures. Treatment of αA-crystallin at high temperatures induced larger oliogomers with higher hydrophobic exposure. Both heat-treated and untreated αA-crystallin could insert into lipid monolayer directly as revealed by monolayer surface pressure experiments. Heat-treatment facilitated the membrane insertion of αA-crystallin and increased the membrane-bound fraction in the cells. The membrane-binding ability of αA-crystallin could be altered by cataract-causing mutations R116C, R116H and Y118D. Our results suggested that the irreversible changes in oligomer size induced by various stresses might promote the membrane association of αA-crystallin and therefore might play a role in aged cataract. Alternations in the membrane binding ability of α-crystallins might be important to the understanding of both aged and congenital cataracts.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Animals; Cataract; Cattle; Cell Membrane; Chromatography; Crystallins; DNA, Complementary; Heat-Shock Proteins; HeLa Cells; Humans; Lipids; Microscopy, Fluorescence; Mutation; Phosphatidylserines; Pressure; Protein Binding; Protein Structure, Quaternary; Protein Structure, Secondary; Serum Albumin, Bovine; Temperature