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M Jiang, Y Wang, A Dhingra, N Vardi, L Birnbaumer; Go1 is Required for the Signal Transduction in the ON-Bipolar Cell . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2918.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Bipolar cells are the secondary neurons in the retina that play a vital role in the processing of visual information. Through their synaptic connections, these cells influence the signaling between photoreceptors and ganglion cells. Bipolar cells obtain sensory information from the neurotransmitter, glutamate, released from photoreceptors. Activation of metabotropic glutamate receptors 6 (mGluR6) by glutamate triggers a G-protein transduction cascade resulting in hyperpolarization of the bipolar cell membrane potential, that in turn regulates ganglion cells firing. Activities of photoreceptors and bipolar cells can be characterized by a- and b- waves of an electroretinogram (ERG), respectively. The molecular basis of the signal transduction in bipolar cells remains to be established. Methods: Using homologous recombination, Go α gene has been inactivated in the mice. The b-wave of the ERG was severely diminished in these mutant mice. Via alternative splicing, two isoforms, Go1α and Go2α are generated from the Goα locus. To dissect the function of each isoform, subtype-specific gene knockouts of Go1α and Go2α have been made. Results: Surprisingly, only Go1α -/-, but not Go2α -/-, mice lose the b-wave of the ERG. This suggests that Go1 selectively couples to mGluR6 and transmits this signal into bipolar cells. Conclusion: Our studies provide the first genetic evidence that the heterotrimeric GTP-binding protein Go, specifically Go1 is required for signal transduction in the retinal ON-bipolar cells.
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