Arvcf Prevents Age-Dependent Cataracts by Stabilizing Adherens Junctions and Cytoskeletal Proteins
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Date
2024-03
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Abstract
The eye lens focuses light paths onto the retina to produce a clear, unobstructed image for optimal vision. However, cellular disruptions can lead to cataracts, a lens disease caused by a loss of transparency. Despite age being the highest risk factor for cataract development, the molecular changes that occur between a young, clear lens to an aged, opaque lens remain relatively unknown. We have demonstrated that genetic ablation of a critical component of adherens junctions, Arvcf, leads to premature cataracts in mice. As this suggests that the loss of Arvcf exacerbates a molecular process in aging, we hypothesize that lens transparency is dependent upon stable cell adhesion in the membrane cytoskeleton. To test this, we compared control and Arvcf-deficient mouse lenses using proteomic and histological methods. Co-immunoprecipitation experiments demonstrate that Arvcf is required for adherens junctional protein associated with N-Cadherin. We also identified novel cytoskeletal and intermediate filaments that associate with Arvcf and N-Cadherin. Immunofluorescent spinning disk confocal microscopy of N-Cadherin, Ankyrin-B, and α-II spectrin show that Arvcf is likely required for maintaining protrusive membrane localization of these associated proteins. Together, these data suggest that the loss of adhesion and cytoskeletal protein association is a biomarker in the aging cataract.
Description
Biological Sciences: 2nd Place (The Ohio State University Edward F. Hayes Advanced
Research Forum)
Keywords
Lens, Adherens junction, Cataract, Arvcf, N-Cadherin, Cytoskeleton