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Hari Ramakrishnan, Anuradha Dhingra, Marie E Fina, Arkady Lyubarsky, Sergei Nikonov, Noga Vardi; Differential Function of Gγ13 in Rod Bipolar and ON Cone Bipolar Cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4169.
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© ARVO (1962-2015); The Authors (2016-present)
Glutamate released from photoreceptors in the dark activates the mGluR6 receptor in ON bipolar cells; this leads to activation of Go, closure of TRPM1 channel, and cell’s hyperpolarization. A flash of light decreases glutamate in the cleft; this inactivates Go, a process that is facilitated by GTPase activating proteins. It is now known that Go is comprised of Gαo1 (with minor contribution from Gαo2) and Gβ3, but the Gγ subunit was not identified. Localization studies suggest that Gγ13 is the partner of Gβ3, but no functional data are present.
To test the function of Gγ13, we generated a Gng13-null mouse and performed ERG recordings and immunocytochemical staining.
We found that the amplitude of the scotopic ERG b-wave in the Gng13-null mice was about half of that in the wild type. The implicit time of the scotopic ERG b-wave was increased, especially in response to low intensities. Furthermore, examination of ERG b-wave at different age groups showed a progressive decline in the amplitude of the scotopic ERG b-wave relative to the WT. In contrast, the photopic ERG b-wave was hardly affected at any age. Immunostaining for the GTPase Activating Proteins RGS11, R9AP and Gβ5 showed a significant two-fold reduction in staining intensity in the dendritic tips of rod bipolar cells and no effect on dendritic tips of ON cone bipolar cells. Similarly, staining for Gβ3 was reduced more profoundly in rod bipolar cells than in cone bipolar cells. Staining for Gαo, mGluR6, TRPM1, and PKC-α were only slightly reduced in the Gng13-null mouse. Analysis of ON bipolar cDNA library showed that the mRNAs for Gγ5, Gγ10 and Gγ11 are expressed. Quantitative RT-PCR of retinal cDNA showed greater values for these transcripts in the Gng13-null retinas, but the difference was not significant.
These data suggest that Gγ13 dimerizes with Gβ3, but it contributes to light signaling in rod bipolar cells more than to signaling in ON cone bipolar cells. Furthermore, Gγ13 contributes less than Gβ3 since deletion of Gβ3 dramatically reduced the light response in both rod and ON cone bipolar cells. Although it is possible that other Gγ subunits contribute to mediating mGluR6 coupling in the ON bipolar cascade, our findings suggest that the Gβγ dimer contributes to signaling indirectly via regulating expression of other cascade elements.
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