title: An allosteric regulator of R7-RGS proteins influences light-evoked activity and glutamatergic waves in the inner retina.
abstract: In the outer retina, G protein-coupled receptor (GPCR) signaling mediates phototransduction and synaptic transmission between photoreceptors and ON bipolar cells. In contrast, the functions of modulatory GPCR signaling networks in the inner retina are less well understood. We addressed this question by determining the consequences of augmenting modulatory Gi/o signaling driven by endogenous transmitters. This was done by analyzing the effects of genetically ablating the R7 RGS-binding protein (R7BP), a membrane-targeting protein and positive allosteric modulator of R7-RGS (regulator of the G protein signaling 7) family that deactivates Gi/oα subunits. We found that R7BP is expressed highly in starburst amacrine cells and retinal ganglion cells (RGCs). As indicated by electroretinography and multielectrode array recordings of adult retina, ablation of R7BP preserved outer retina function, but altered the firing rate and latency of ON RGCs driven by rods and cones but not rods alone. In developing retina, R7BP ablation increased the burst duration of glutamatergic waves whereas cholinergic waves were unaffected. This effect on glutamatergic waves did not result in impaired segregation of RGC projections to eye-specific domains of the dorsal lateral geniculate nucleus. R7BP knockout mice exhibited normal spatial contrast sensitivity and visual acuity as assessed by optomotor reflexes. Taken together these findings indicate that R7BP-dependent regulation of R7-RGS proteins shapes specific aspects of light-evoked and spontaneous activity of RGCs in mature and developing retina.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Cain
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Bradly Q
authors.initials: BQ
authors.lastname: Vo
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kolesnikov
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Kefalov
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Culican
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kerschensteiner
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Kendall J
authors.initials: KJ
authors.lastname: Blumer
mesh_terms: D000200:Action Potentials / Q000528:radiation effects; D000494:Allosteric Regulation / Q000528:radiation effects; D025042:Amacrine Cells / Q000378:metabolism / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D002794:Choline / Q000378:metabolism; D015350:Contrast Sensitivity / Q000528:radiation effects; D017353:Gene Deletion; D005971:Glutamates / Q000378:metabolism*; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D020710:RGS Proteins / Q000172:deficiency / Q000378:metabolism*; D012160:Retina / Q000378:metabolism* / Q000528:radiation effects*; D051245:Retinal Bipolar Cells / Q000378:metabolism / Q000528:radiation effects; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000528:radiation effects; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism; D050819:Transcription Factor Brn-3A / Q000378:metabolism; D014792:Visual Acuity / Q000528:radiation effects
chemical_list: D005971:Glutamates; C494189:Pou4f1 protein, mouse; C499440:R7BP protein, mouse; D020710:RGS Proteins; D050819:Transcription Factor Brn-3A; D002794:Choline