Modulation of mouse rod response decay by rhodopsin kinase and recoverin

Ching Kang Chen, Michael L. Woodruff, Frank S. Chen, Yenlin Chen, Marianne C. Cilluffo, Daniel Tranchina, Gordon L. Fain

Research output: Contribution to journalArticle

Abstract

Light isomerizes 11-cis-retinal in a retinal rod and produces an active form of rhodopsin (Rh*) that binds to the G-protein transducin and activates the phototransduction cascade. Rh* is turned off by phosphorylation by rhodopsin kinase [G-protein-coupled receptor kinase 1 (GRK1)] and subsequent binding of arrestin. To evaluate the role of GRK1 in rod light response decay, we have generated the transgenic mouse RKS561L in which GRK1, which is normally present at only 2-3% of rhodopsin, is overexpressed by ~ 12-fold. Overexpression of GRK1 increases the rate of Rh* phosphorylation and reduces the exponential decay constant of the response (TREC) and the limiting time constant (tD) both by ~30%; these decreases are highly significant. Similar decreases are produced in Rv-/- rods, in which the GRK1-binding protein recoverin has been genetically deleted. These changes in response decay are produced by acceleration of light-activated phosphodiesterase (PDE*) decay rather than Rh* decay, because light-activated PDE* decay remains rate limiting for response decay in both RKS561L and Rv-/- rods. A model incorporating an effect of GRK1 on light-activated PDE* decay rate can satisfactorily account for the changes in response amplitude and waveform. Modulation of response decay in background light is nearly eliminated by deletion of recoverin. Our experiments indicate that rhodopsin kinase and recoverin, in addition to their well-known role in regulating the turning off of Rh*, can also modulate the decay of light-activated PDE*, and the effects of these proteins on light-activated PDE* decay may be responsible for the quickening of response recovery in background light.

Original languageEnglish (US)
Pages (from-to)15998-16006
Number of pages9
JournalJournal of Neuroscience
Volume32
Issue number45
DOIs
StatePublished - Nov 7 2012

Fingerprint

G-Protein-Coupled Receptor Kinase 1
Recoverin
Rhodopsin
Phosphoric Diester Hydrolases
Light
Phosphorylation
Transducin
Retinaldehyde
Light Signal Transduction
Arrestin
Retinal Rod Photoreceptor Cells
GTP-Binding Proteins
Transgenic Mice
Carrier Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chen, C. K., Woodruff, M. L., Chen, F. S., Chen, Y., Cilluffo, M. C., Tranchina, D., & Fain, G. L. (2012). Modulation of mouse rod response decay by rhodopsin kinase and recoverin. Journal of Neuroscience, 32(45), 15998-16006. https://doi.org/10.1523/JNEUROSCI.1639-12.2012

Modulation of mouse rod response decay by rhodopsin kinase and recoverin. / Chen, Ching Kang; Woodruff, Michael L.; Chen, Frank S.; Chen, Yenlin; Cilluffo, Marianne C.; Tranchina, Daniel; Fain, Gordon L.

In: Journal of Neuroscience, Vol. 32, No. 45, 07.11.2012, p. 15998-16006.

Research output: Contribution to journalArticle

Chen, CK, Woodruff, ML, Chen, FS, Chen, Y, Cilluffo, MC, Tranchina, D & Fain, GL 2012, 'Modulation of mouse rod response decay by rhodopsin kinase and recoverin', Journal of Neuroscience, vol. 32, no. 45, pp. 15998-16006. https://doi.org/10.1523/JNEUROSCI.1639-12.2012
Chen, Ching Kang ; Woodruff, Michael L. ; Chen, Frank S. ; Chen, Yenlin ; Cilluffo, Marianne C. ; Tranchina, Daniel ; Fain, Gordon L. / Modulation of mouse rod response decay by rhodopsin kinase and recoverin. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 45. pp. 15998-16006.
@article{99af1841ae4c44a394d91e533775c661,
title = "Modulation of mouse rod response decay by rhodopsin kinase and recoverin",
abstract = "Light isomerizes 11-cis-retinal in a retinal rod and produces an active form of rhodopsin (Rh*) that binds to the G-protein transducin and activates the phototransduction cascade. Rh* is turned off by phosphorylation by rhodopsin kinase [G-protein-coupled receptor kinase 1 (GRK1)] and subsequent binding of arrestin. To evaluate the role of GRK1 in rod light response decay, we have generated the transgenic mouse RKS561L in which GRK1, which is normally present at only 2-3{\%} of rhodopsin, is overexpressed by ~ 12-fold. Overexpression of GRK1 increases the rate of Rh* phosphorylation and reduces the exponential decay constant of the response (TREC) and the limiting time constant (tD) both by ~30{\%}; these decreases are highly significant. Similar decreases are produced in Rv-/- rods, in which the GRK1-binding protein recoverin has been genetically deleted. These changes in response decay are produced by acceleration of light-activated phosphodiesterase (PDE*) decay rather than Rh* decay, because light-activated PDE* decay remains rate limiting for response decay in both RKS561L and Rv-/- rods. A model incorporating an effect of GRK1 on light-activated PDE* decay rate can satisfactorily account for the changes in response amplitude and waveform. Modulation of response decay in background light is nearly eliminated by deletion of recoverin. Our experiments indicate that rhodopsin kinase and recoverin, in addition to their well-known role in regulating the turning off of Rh*, can also modulate the decay of light-activated PDE*, and the effects of these proteins on light-activated PDE* decay may be responsible for the quickening of response recovery in background light.",
author = "Chen, {Ching Kang} and Woodruff, {Michael L.} and Chen, {Frank S.} and Yenlin Chen and Cilluffo, {Marianne C.} and Daniel Tranchina and Fain, {Gordon L.}",
year = "2012",
month = "11",
day = "7",
doi = "10.1523/JNEUROSCI.1639-12.2012",
language = "English (US)",
volume = "32",
pages = "15998--16006",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "45",

}

TY - JOUR

T1 - Modulation of mouse rod response decay by rhodopsin kinase and recoverin

AU - Chen, Ching Kang

AU - Woodruff, Michael L.

AU - Chen, Frank S.

AU - Chen, Yenlin

AU - Cilluffo, Marianne C.

AU - Tranchina, Daniel

AU - Fain, Gordon L.

PY - 2012/11/7

Y1 - 2012/11/7

N2 - Light isomerizes 11-cis-retinal in a retinal rod and produces an active form of rhodopsin (Rh*) that binds to the G-protein transducin and activates the phototransduction cascade. Rh* is turned off by phosphorylation by rhodopsin kinase [G-protein-coupled receptor kinase 1 (GRK1)] and subsequent binding of arrestin. To evaluate the role of GRK1 in rod light response decay, we have generated the transgenic mouse RKS561L in which GRK1, which is normally present at only 2-3% of rhodopsin, is overexpressed by ~ 12-fold. Overexpression of GRK1 increases the rate of Rh* phosphorylation and reduces the exponential decay constant of the response (TREC) and the limiting time constant (tD) both by ~30%; these decreases are highly significant. Similar decreases are produced in Rv-/- rods, in which the GRK1-binding protein recoverin has been genetically deleted. These changes in response decay are produced by acceleration of light-activated phosphodiesterase (PDE*) decay rather than Rh* decay, because light-activated PDE* decay remains rate limiting for response decay in both RKS561L and Rv-/- rods. A model incorporating an effect of GRK1 on light-activated PDE* decay rate can satisfactorily account for the changes in response amplitude and waveform. Modulation of response decay in background light is nearly eliminated by deletion of recoverin. Our experiments indicate that rhodopsin kinase and recoverin, in addition to their well-known role in regulating the turning off of Rh*, can also modulate the decay of light-activated PDE*, and the effects of these proteins on light-activated PDE* decay may be responsible for the quickening of response recovery in background light.

AB - Light isomerizes 11-cis-retinal in a retinal rod and produces an active form of rhodopsin (Rh*) that binds to the G-protein transducin and activates the phototransduction cascade. Rh* is turned off by phosphorylation by rhodopsin kinase [G-protein-coupled receptor kinase 1 (GRK1)] and subsequent binding of arrestin. To evaluate the role of GRK1 in rod light response decay, we have generated the transgenic mouse RKS561L in which GRK1, which is normally present at only 2-3% of rhodopsin, is overexpressed by ~ 12-fold. Overexpression of GRK1 increases the rate of Rh* phosphorylation and reduces the exponential decay constant of the response (TREC) and the limiting time constant (tD) both by ~30%; these decreases are highly significant. Similar decreases are produced in Rv-/- rods, in which the GRK1-binding protein recoverin has been genetically deleted. These changes in response decay are produced by acceleration of light-activated phosphodiesterase (PDE*) decay rather than Rh* decay, because light-activated PDE* decay remains rate limiting for response decay in both RKS561L and Rv-/- rods. A model incorporating an effect of GRK1 on light-activated PDE* decay rate can satisfactorily account for the changes in response amplitude and waveform. Modulation of response decay in background light is nearly eliminated by deletion of recoverin. Our experiments indicate that rhodopsin kinase and recoverin, in addition to their well-known role in regulating the turning off of Rh*, can also modulate the decay of light-activated PDE*, and the effects of these proteins on light-activated PDE* decay may be responsible for the quickening of response recovery in background light.

UR - http://www.scopus.com/inward/record.url?scp=84868580133&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868580133&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1639-12.2012

DO - 10.1523/JNEUROSCI.1639-12.2012

M3 - Article

C2 - 23136436

AN - SCOPUS:84868580133

VL - 32

SP - 15998

EP - 16006

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 45

ER -