Purchase this article with an account.
MM Nguyen, AE Griep; Possible Role for PDZ Domain-Containing Proteins in Lens Development . Invest. Ophthalmol. Vis. Sci. 2002;43(13):465.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Membrane-associated guanylate kinases (MAGUKs) that contain the PDZ protein-protein interaction domain are necessary for proper maintenance of cell junctions, cell polarity and proliferation. Among these PDZ domain-containing proteins are a class of Drosophila tumor suppressors that include DLG, Scrib, and LGL. Null mutations of these genes in Drosophila lead to hyperplastic growth and loss of cell-cell adhesion and polarity in embryonic, imaginal disc, and follicular epithelia. Interestingly, we see a remarkably similar phenotype in lenses of K14E6 mice that express HPV16-E6, a viral oncogene, in the epithelium and transition zone. E6 has been shown to bind and inactivate several proteins including the PDZ domain-containing proteins such as DLG and Scrib. Using RT-PCR and in situ hybridization, we have learned that DLG and LGL are expressed in the mouse lens. Purpose: To determine if E6 binding to PDZ proteins was the basis for the K14E6 lens phenotype, we generated transgenic mice expressing E6 mutants that either retain or lose the ability to bind PDZ domain-containing proteins. Methods and Results: The mutants used in this study were the E6I128T mutant, which fails to bind several proteins, among them a ubiquitin ligase and paxillin, but retains the ability to bind PDZ proteins; and the E6D146-151 mutant which fails to bind PDZ proteins. Expression levels of the mutant E6 transgenes were similar to those seen in the lenses of the wildtype E6 mice. Histological, BrdU incorporation, and TUNEL analyses of the lenses in these mice showed that K14E6I28T mice retained most of the wildtype E6 lens phenotype while lenses of the K14E6D146-151 mice only display a slight increase in proliferation in the epithelium. Conclusions: These results suggest that PDZ domain-containing proteins may be required in the epithelium and transition zone and that those proteins bound by the I128 region may only play a minor role. Taken together, these data provide evidence for a role for PDZ domain-containing proteins in lens development.
This PDF is available to Subscribers Only