Up-regulation of tau, a brain microtubule-associated protein, in lens cortical fractions of aged αA-, αB-, and αA/B-crystallin knockout mice

Purpose: α-Crystallin is expressed at high levels in the lens in a complex of αA- and αB-crystallin subunits in 3:1 molar ratios, and is known to maintain the solubility of unpolymerized tubulin and enhance the resistance of microtubules to depolymerization, but its effect on proteins classically associated with microtubule stability (microtubule associated proteins) in the lens is unknown. In the present study we examined the expression of the brain microtubule associated protein tau in lenses of α-crystallin gene knockout mice. Methods: Quantitative RT-PCR, immunoblotting, cryo-immunoelectron microscopic and immunohistochemical methods were used to characterize the expression of tau in the lenses of αA⁺-, αB⁺ -, and αA/B⁺ -crystallin mice. Results: Immunoreactivity to tau, a 45-66 kDa brain microtubule associated protein that has been best characterized in neurons and neuronal pathologies, was uniquely upregulated in lens cortical fiber cells with aging and was associated with the microtubule fraction of αA^-/--, αB^-/--, and αA/B^-/--crystallin mouse lenses, but was undetectable in wild type lenses. Quantitative RT-PCR analysis further showed an upregulation of tau transcripts in αA^-/-- and αA/B^-/- -crystallin lenses. Brain microtubule fractions served as a positive control for tau in these experiments. An increase in phosphorylation of tau was detected in αA^-/-- and αB^-/--crystallin brain proteins. Conclusions: Although tau aggregation and αB-crystallin expression have been shown to increase in neurodegenerative diseases, surprisingly tau expression increases in the α-crystallin knockout lenses, suggesting that αA- and αB-crystallins are potentially important regulators of tau expression in lens.