TY - JOUR
T1 - Gβ5-RGS complexes co-localize with mGluR6 in retinal ON-bipolar cells
AU - Morgans, Catherine W.
AU - Wensel, Theodore G.
AU - Brown, R. Lane
AU - Perez-Leon, Jorge A.
AU - Bearnot, Ben
AU - Duvoisin, Robert M.
PY - 2007/11
Y1 - 2007/11
N2 - 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.
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.
KW - Metabotropic glutamate receptor
KW - Mouse
KW - Retina
KW - Ribbon synapse
KW - Synaptic transmission
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U2 - 10.1111/j.1460-9568.2007.05867.x
DO - 10.1111/j.1460-9568.2007.05867.x
M3 - Article
C2 - 18001285
AN - SCOPUS:36148946423
SN - 0953-816X
VL - 26
SP - 2899
EP - 2905
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 10
ER -