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Vasanth Rao, Rupalatha Maddala, Anne R Bresnick, ; S100A4, a Calcium Binding Protein and Regulator of Myosin IIA Assembly is required for Lens Architecture and Transparency. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2642.
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© ARVO (1962-2015); The Authors (2016-present)
To explore the role of S100A4, a calcium binding protein and regulator of Myosin IIA filament assembly in lens fiber cell migration, architecture and transparency.
The expression and distribution profile of S100A4 in the developing and adult mouse lens was determined by immunofluorescence, immunoblotting and mass spectrometry analyses. The role of S100A4 in lens integrity and transparency was evaluated by histology using S100A4-deficient mice (C57BL/6 genetic background).
Immunofluorescence-based analysis of S100A4 distribution revealed abundant expression in the lens relative to other ocular tissues. In the developing mouse lens, S100A4 expression was induced at embryonic day 13.5 in a fiber cell specific manner. While S100A4 expression had begun to decline in the mature primary lens fibers, robust immunofluorescence was noted in the differentiating secondary lens fibers in day 1 lenses. In P21 and adult mouse lenses, S100A4 exhibited a rather discrete localization to the elongating secondary fibers. Immunoblotting analysis indicated a lens differentiation- and maturation-dependent increase in S100A4 protein levels. Our preliminary data using S100A4 null mice revealed that 6 month-old mice exhibit mature cataracts. Histological analyses revealed that eyes derived from S100A4 null mice exhibited age-dependent progressive abnormalities in lens fiber cell shape and organization, starting from 10 weeks of age. The six month-old S100A4 null lenses exhibited extensive accumulation of large vacuoles and disruption of fiber cell organization in association with lens opacity.
This preliminary study reveals that expression of S100A4, a member of the S100 family of Ca2+-binding proteins and a well-characterized regulator of myosin IIA filament assembly and cell migration, is induced during lens fiber cell differentiation. In adult lenses, S100A4 localizes primarily to the elongating secondary fiber cells. Importantly, the disruption in lens fiber cell organization and cataract formation in S100A4 deficient lenses uncovers an essential role for this protein in lens fiber cell organization and transparency.
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