Cones respond to light in the absence of transducin β subunit

Sergei S. Nikonov, Arkady Lyubarsky, Marie E. Fina, Elena S. Nikonova, Abhishek Sengupta, Chidambaram Chinniah, Xi Qin Ding, Robert G. Smith, Edward N Pugh Jr, Noga Vardi, Anuradha Dhingra

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)5182-5194
Number of pages13
JournalJournal of Neuroscience
Volume33
Issue number12
DOIs
StatePublished - Mar 20 2013

Fingerprint

Transducin
Light Signal Transduction
Light
Heterotrimeric GTP-Binding Proteins
Photophobia
Phosphoric Diester Hydrolases

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nikonov, S. S., Lyubarsky, A., Fina, M. E., Nikonova, E. S., Sengupta, A., Chinniah, C., ... Dhingra, A. (2013). Cones respond to light in the absence of transducin β subunit. Journal of Neuroscience, 33(12), 5182-5194. https://doi.org/10.1523/JNEUROSCI.5204-12.2013

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 journalArticle

Nikonov, SS, Lyubarsky, A, Fina, ME, Nikonova, ES, Sengupta, A, Chinniah, C, Ding, XQ, Smith, RG, Pugh Jr, EN, Vardi, N & Dhingra, A 2013, 'Cones respond to light in the absence of transducin β subunit', Journal of Neuroscience, vol. 33, no. 12, pp. 5182-5194. https://doi.org/10.1523/JNEUROSCI.5204-12.2013
Nikonov SS, Lyubarsky A, Fina ME, Nikonova ES, Sengupta A, Chinniah C et al. Cones respond to light in the absence of transducin β subunit. Journal of Neuroscience. 2013 Mar 20;33(12):5182-5194. https://doi.org/10.1523/JNEUROSCI.5204-12.2013
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. / Cones respond to light in the absence of transducin β subunit. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 12. pp. 5182-5194.
@article{8badf29fd949441e8296415725753073,
title = "Cones respond to light in the absence of transducin β subunit",
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.",
author = "Nikonov, {Sergei S.} and Arkady Lyubarsky and Fina, {Marie E.} and Nikonova, {Elena S.} and Abhishek Sengupta and Chidambaram Chinniah and Ding, {Xi Qin} and Smith, {Robert G.} and {Pugh Jr}, {Edward N} and Noga Vardi and Anuradha Dhingra",
year = "2013",
month = "3",
day = "20",
doi = "10.1523/JNEUROSCI.5204-12.2013",
language = "English (US)",
volume = "33",
pages = "5182--5194",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "12",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=84877092933&partnerID=8YFLogxK

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 -