Gβ5-RGS complexes co-localize with mGluR6 in retinal ON-bipolar cells

Catherine Morgans, Theodore G. Wensel, R. Lane Brown, Jorge A. Perez-Leon, Ben Bearnot, Robert Duvoisin

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

The time course of G-protein-coupled responses is largely determined by the kinetics of GTP hydrolysis by the G protein α subunit, which is accelerated by interaction with regulator of G-protein signaling (RGS) proteins. Light responses of ON-bipolar cells of the vertebrate retina require rapid inactivation of the G protein Gαo, which is activated in the dark by metabotropic glutamate receptor, mGluR6, in their dendritic tips. It is not yet known, however, which RGS protein(s) might be responsible for rapid inactivation kinetics. By immunofluorescence and co-immunoprecipitation, we have identified complexes of the Gαo-selective RGS proteins RGS7 and RGS11, with their obligate binding partner, Gβ5, that are localized to the dendritic tips of murine rod and cone ON-bipolar cells, along with mGluR6. Experiments using pre- and post-synaptic markers, and a dissociated bipolar cell preparation, clearly identified the location of these complexes as the ON-bipolar cell dendritic tips and not the adjacent photoreceptor terminals or horizontal cell dendrites. In mice lacking mGluR6, the distribution of RGS11, RGS7 and Gβ5 shifts away from the dendritic tips, implying a functional relationship with mGluR6. The precise co-localization of Gβ5-RGS7 and Gβ5-RGS11 with mGluR6, and the dependence of localization on the presence of mGluR6, suggests that Gβ5-RGS7 and Gβ5-RGS11 function specifically in the mGluR6 signal transduction pathway, where they may stimulate the GTPase activity of Gαo, thus accelerating the ON-bipolar cell light response, in a manner analogous to the acceleration of photoreceptor light responses by the Gβ5-RGS9-1 complex.

Original languageEnglish (US)
Pages (from-to)2899-2905
Number of pages7
JournalEuropean Journal of Neuroscience
Volume26
Issue number10
DOIs
StatePublished - Nov 2007

Fingerprint

Retinal Bipolar Cells
GTP-Binding Protein Regulators
RGS Proteins
GTP-Binding Proteins
Light
Gi-Go GTP-Binding Protein alpha Subunits
Vertebrate Photoreceptor Cells
Metabotropic Glutamate Receptors
GTP Phosphohydrolases
Protein Subunits
Dendrites
Guanosine Triphosphate
metabotropic glutamate receptor 6
Immunoprecipitation
Dendritic Cells
Fluorescent Antibody Technique
Vertebrates
Retina
Signal Transduction
Hydrolysis

Keywords

  • Metabotropic glutamate receptor
  • Mouse
  • Retina
  • Ribbon synapse
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Gβ5-RGS complexes co-localize with mGluR6 in retinal ON-bipolar cells. / Morgans, Catherine; Wensel, Theodore G.; Brown, R. Lane; Perez-Leon, Jorge A.; Bearnot, Ben; Duvoisin, Robert.

In: European Journal of Neuroscience, Vol. 26, No. 10, 11.2007, p. 2899-2905.

Research output: Contribution to journalArticle

Morgans, Catherine ; Wensel, Theodore G. ; Brown, R. Lane ; Perez-Leon, Jorge A. ; Bearnot, Ben ; Duvoisin, Robert. / Gβ5-RGS complexes co-localize with mGluR6 in retinal ON-bipolar cells. In: European Journal of Neuroscience. 2007 ; Vol. 26, No. 10. pp. 2899-2905.
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AU - Morgans, Catherine

AU - Wensel, Theodore G.

AU - Brown, R. Lane

AU - Perez-Leon, Jorge A.

AU - Bearnot, Ben

AU - Duvoisin, Robert

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AB - The time course of G-protein-coupled responses is largely determined by the kinetics of GTP hydrolysis by the G protein α subunit, which is accelerated by interaction with regulator of G-protein signaling (RGS) proteins. Light responses of ON-bipolar cells of the vertebrate retina require rapid inactivation of the G protein Gαo, which is activated in the dark by metabotropic glutamate receptor, mGluR6, in their dendritic tips. It is not yet known, however, which RGS protein(s) might be responsible for rapid inactivation kinetics. By immunofluorescence and co-immunoprecipitation, we have identified complexes of the Gαo-selective RGS proteins RGS7 and RGS11, with their obligate binding partner, Gβ5, that are localized to the dendritic tips of murine rod and cone ON-bipolar cells, along with mGluR6. Experiments using pre- and post-synaptic markers, and a dissociated bipolar cell preparation, clearly identified the location of these complexes as the ON-bipolar cell dendritic tips and not the adjacent photoreceptor terminals or horizontal cell dendrites. In mice lacking mGluR6, the distribution of RGS11, RGS7 and Gβ5 shifts away from the dendritic tips, implying a functional relationship with mGluR6. The precise co-localization of Gβ5-RGS7 and Gβ5-RGS11 with mGluR6, and the dependence of localization on the presence of mGluR6, suggests that Gβ5-RGS7 and Gβ5-RGS11 function specifically in the mGluR6 signal transduction pathway, where they may stimulate the GTPase activity of Gαo, thus accelerating the ON-bipolar cell light response, in a manner analogous to the acceleration of photoreceptor light responses by the Gβ5-RGS9-1 complex.

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