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RGS7 and -11 complexes accelerate the ON-bipolar cell light response

Jianmei Zhang1, Brett G Jeffrey, Catherine W Morgans

  • 1Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington, USA.

Investigative Ophthalmology & Visual Science
|October 3, 2009
PubMed
Abstract

Insights

Regulator of G protein signaling 11 (RGS11) is crucial for deactivating G protein Go in retinal ON-bipolar cells. Loss of RGS11, and to a lesser extent RGS7, delays visual signaling and alters retinal light responses.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Vision Science

Background:

  • The light response in retinal ON-bipolar cells (ON-BPCs) begins with the deactivation of the metabotropic glutamate receptor mGluR6 and the G protein Go.
  • Regulator of G protein signaling (RGS) proteins typically accelerate G protein signaling cascades by interacting with the G protein alpha subunit.

Purpose of the Study:

  • To investigate the role of RGS7 and RGS11 in the function of retinal ON-BPCs.
  • To determine if RGS7 and/or RGS11 accelerate the deactivation of the G protein Go in ON-BPCs.

Main Methods:

  • Immunofluorescence confocal microscopy was used to compare retinas from wild-type (WT) mice with those lacking RGS11 (RGS11(-/-)), RGS7 (RGS7(Delta/Delta)), or both.
  • Electroretinogram (ERG) was employed to measure the overall retinal light response.
  • Whole-cell patch-clamp electrophysiology recorded the kinetics of simulated light responses from individual rod bipolar cells.

Main Results:

  • Reduced levels of RGS7 RGS interaction partners (Gbeta5 and R9AP) were observed in the outer plexiform layer of RGS11(-/-) and RGS7(Delta/Delta)/RGS11(-/-) mice.
  • ERG recordings in RGS11(-/-) and RGS7(Delta/Delta)/RGS11(-/-) mice showed delayed b-wave rising phases, larger photopic b-wave amplitudes, and increased scotopic threshold response sensitivity.
  • Patch-clamp recordings revealed a 25-ms delay in the onset of the ON-BPC response in RGS7(Delta/Delta)/RGS11(-/-) mice compared to WT, while RGS7(Delta/Delta) mice showed normal ERG.
  • The ERG of RGS7(Delta/Delta) mice was normal, indicating RGS11 is the primary player.

Conclusions:

  • RGS11 is essential for the deactivation of Galphao, a critical step preceding the activation of the depolarizing current in ON-BPCs.
  • RGS7 also contributes to this process, as evidenced by more pronounced changes in mice lacking both RGS7 and RGS11 compared to those lacking only RGS11.

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