Two R7 regulator of G-protein signaling proteins shape retinal bipolar cell signaling.
RGS7, RGS11, and their binding partner Gbeta5 are localized to the dendritic tips of retinal ON bipolar cells (ON-BPC), where mGluR6 responds to glutamate released from photoreceptor terminals by activation of the RGS7/RGS11 substrate, Galphao. To determine their functions in retinal signaling, we investigated cell-specific expression patterns of RGS7 and RGS11 by immunostaining, and measured light responses by electroretinography in mice with targeted disruptions of the genes encoding them. RGS7 staining is present in dendritic tips of all rod ON-BPC, but missing in those for subsets of cone ON-BPC, whereas the converse was true for RGS11 staining. Genetic disruption of either RGS7 or RGS11 produced delays in the ON-BPC-derived electroretinogram b-wave, but no changes in the photoreceptor-derived a-wave. Homozygous RGS7 mutant mice had delays in rod-driven b-waves, whereas RGS11 mutant mice had delays in rod-driven, and especially in cone-driven b-waves. The b-wave delays were further enhanced in mice homozygous for both RGS7 and RGS11 gene disruptions. Thus, RGS7 and RGS11 act in parallel to regulate the kinetics of ON bipolar cell responses, with differential impacts on the rod and cone pathways.
Mojumder
Deb Kumar
DK
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Qian
Yan
Y
Wensel
Theodore G
TG
D000221:Adaptation, Ocular / Q000187:drug effects / Q000235:genetics; D000818:Animals; D003712:Dendrites / Q000378:metabolism; D004585:Electrooculography / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011493:Protein Kinase C / Q000378:metabolism; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D005136:Eye Proteins; D044387:GTP-Binding Protein beta Subunits; D020690:GTPase-Activating Proteins; D020710:RGS Proteins; D018094:Receptors, Metabotropic Glutamate; C485693:Rgs11 protein, mouse; C492038:Rgs7 protein, mouse; C113897:metabotropic glutamate receptor 6; D005680:gamma-Aminobutyric Acid; D011493:Protein Kinase C; D019206:GTP-Binding Protein alpha Subunits, Gi-Go