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Adam G. Neinstein, Anuradha Dhingra, Marie E. Fina, Noga Vardi; Absence of Gβ3 from ON Bipolar Cells Reduces Expression of Postsynaptic and Presynaptic Proteins. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4315.
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© ARVO (1962-2015); The Authors (2016-present)
A recent study in our lab showed that elimination of Gβ3, a G protein subunit expressed in ON bipolar cells, greatly alters the expression of most known mGluR6 cascade elements. Furthermore, examination of the ultrastructure of the rod synaptic complex showed greatly reduced number of invaginating rod bipolar cells. In this study we examined the role of Gβ3 in controlling the expression of presynaptic and postsynaptic elements of the photoreceptor synapse.
Immunostaining was performed on sections of Gβ3 knockout and wild-type C57BL/6 mouse retina with antibodies against Cacna-1s, dystrophin and β-dystroglycan. Animals of different ages (6 weeks and 7 months) were used, in order to examine the effects of aging on possible retinal degeneration in the knockout.
In the wild type retinas, staining for the Ca2+ channel subunit Cacna-1s was restricted to the dendritic tips of ON bipolar cells. In the Gβ3-deficient mice, this staining was almost completely eliminated. On the presynaptic side, staining for dystrophin and β-dystroglycan, a dystrophin-associated glycoprotein, was also punctate, and the puncta were present on the photoreceptor terminals in close apposition to mGluR6. In the Gβ3 knockout, expression of both dystrophin and β-dystroglycan was heavily downregulated. Quantifying expression in the OPL showed that dystrophin staining was reduced by ~65% and β-dystroglycan staining by ~58%. Ultrastructurally, we observed many rod terminals that stained darker than their neighbors, presumably showing signs of degeneration. In the older mouse, expression of both dystrophin and β-dystroglycan was reduced to a greater degree and the remaining puncta were sparse.
Gβ3 in ON bipolar cells is necessary not only for maintaining normal expression of certain proteins in rod bipolar cells, but also presynaptically in photoreceptors. Thus, our Gβ3 knockout mouse serves as an interesting example of retrograde signaling and degeneration. Mechanistically, it is possible that dystrophin and β-dystroglycan form complexes with postsynaptic structures on bipolar cells, structures that may be compromised when Gβ3 is not expressed.
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