Abstract
Mammalian cones respond to light by closing a cGMP-gated channel via a cascade that includes a heterotrimeric G-protein, cone transducin, comprising Gαt2, Gβ3 and Gγt2 subunits. The function of Gβγ in this cascade has not been examined. Here, we investigate the role of Gβ3 by assessing cone structure and function in Gβ3-null mouse (Gnb3-/-). We found that Gβ3 is required for the normal expression of its partners, because in the Gnb3-/- cone outer segments, the levels of Gαt2 and Gγt2 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 Gβ 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 Gαt2 level in the cone outer segment, we conclude that activation of Gαt2 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 Gβ3 in cones is to establish optimal levels of transducin heteromer in the outer segment, thereby indirectly contributing to robust response properties.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5182-5194 |
| Number of pages | 13 |
| Journal | Journal of Neuroscience |
| Volume | 33 |
| Issue number | 12 |
| DOIs | |
| State | Published - Mar 20 2013 |
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ASJC Scopus subject areas
- Neuroscience(all)
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Cones respond to light in the absence of transducin β subunit. / Nikonov, Sergei S.; Lyubarsky, Arkady; Fina, Marie E.; Nikonova, Elena S.; Sengupta, Abhishek; Chinniah, Chidambaram; Ding, Xi Qin; Smith, Robert G.; Pugh Jr, Edward N; Vardi, Noga; Dhingra, Anuradha.
In: Journal of Neuroscience, Vol. 33, No. 12, 20.03.2013, p. 5182-5194.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cones respond to light in the absence of transducin β subunit
AU - Nikonov, Sergei S.
AU - Lyubarsky, Arkady
AU - Fina, Marie E.
AU - Nikonova, Elena S.
AU - Sengupta, Abhishek
AU - Chinniah, Chidambaram
AU - Ding, Xi Qin
AU - Smith, Robert G.
AU - Pugh Jr, Edward N
AU - Vardi, Noga
AU - Dhingra, Anuradha
PY - 2013/3/20
Y1 - 2013/3/20
N2 - Mammalian cones respond to light by closing a cGMP-gated channel via a cascade that includes a heterotrimeric G-protein, cone transducin, comprising Gαt2, Gβ3 and Gγt2 subunits. The function of Gβγ in this cascade has not been examined. Here, we investigate the role of Gβ3 by assessing cone structure and function in Gβ3-null mouse (Gnb3-/-). We found that Gβ3 is required for the normal expression of its partners, because in the Gnb3-/- cone outer segments, the levels of Gαt2 and Gγt2 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 Gβ 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 Gαt2 level in the cone outer segment, we conclude that activation of Gαt2 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 Gβ3 in cones is to establish optimal levels of transducin heteromer in the outer segment, thereby indirectly contributing to robust response properties.
AB - Mammalian cones respond to light by closing a cGMP-gated channel via a cascade that includes a heterotrimeric G-protein, cone transducin, comprising Gαt2, Gβ3 and Gγt2 subunits. The function of Gβγ in this cascade has not been examined. Here, we investigate the role of Gβ3 by assessing cone structure and function in Gβ3-null mouse (Gnb3-/-). We found that Gβ3 is required for the normal expression of its partners, because in the Gnb3-/- cone outer segments, the levels of Gαt2 and Gγt2 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 Gβ 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 Gαt2 level in the cone outer segment, we conclude that activation of Gαt2 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 Gβ3 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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UR - http://www.scopus.com/inward/citedby.url?scp=84877092933&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.5204-12.2013
DO - 10.1523/JNEUROSCI.5204-12.2013
M3 - Article
C2 - 23516284
AN - SCOPUS:84877092933
VL - 33
SP - 5182
EP - 5194
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 12
ER -