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Publication : Cones respond to light in the absence of transducin β subunit.

First Author  Nikonov SS Year  2013
Journal  J Neurosci Volume  33
Issue  12 Pages  5182-94
PubMed ID  23516284 Mgi Jnum  J:196593
Mgi Id  MGI:5488842 Doi  10.1523/JNEUROSCI.5204-12.2013
Citation  Nikonov SS, et al. (2013) Cones respond to light in the absence of transducin beta subunit. J Neurosci 33(12):5182-94
abstractText  Mammalian cones respond to light by closing a cGMP-gated channel via a cascade that includes a heterotrimeric G-protein, cone transducin, comprising Galphat2, Gbeta3 and Ggammat2 subunits. The function of Gbetagamma in this cascade has not been examined. Here, we investigate the role of Gbeta3 by assessing cone structure and function in Gbeta3-null mouse (Gnb3(-/-)). We found that Gbeta3 is required for the normal expression of its partners, because in the Gnb3(-/-) cone outer segments, the levels of Galphat2 and Ggammat2 are reduced by fourfold to sixfold, whereas other components of the cascade remain unaltered. Surprisingly, Gnb3(-/-) cones produce stable responses with normal kinetics and saturating response amplitudes similar to that of the wild-type, suggesting that cone phototransduction can function efficiently without a Gbeta subunit. However, light sensitivity was reduced by approximately fourfold in the knock-out cones. Because the reduction in sensitivity was similar in magnitude to the reduction in Galphat2 level in the cone outer segment, we conclude that activation of Galphat2 in Gnb3(-/-) cones proceeds at a rate approximately proportional to its outer segment concentration, and that activation of phosphodiesterase and downstream cascade components is normal. These results suggest that the main role of Gbeta3 in cones is to establish optimal levels of transducin heteromer in the outer segment, thereby indirectly contributing to robust response properties.
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