title: Regulators of G protein signaling RGS7 and RGS11 determine the onset of the light response in ON bipolar neurons.
abstract: The time course of signaling via heterotrimeric G proteins is controlled through their activation by G-protein coupled receptors and deactivation through the action of GTPase accelerating proteins (GAPs). Here we identify RGS7 and RGS11 as the key GAPs in the mGluR6 pathway of retinal rod ON bipolar cells that set the sensitivity and time course of light-evoked responses. We showed using electroretinography and single cell recordings that the elimination of RGS7 did not influence dark-adapted light-evoked responses, but the concurrent elimination of RGS11 severely reduced their magnitude and dramatically slowed the onset of the response. In RGS7/RGS11 double-knockout mice, light-evoked responses in rod ON bipolar cells were only observed during persistent activation of rod photoreceptors that saturate rods. These observations are consistent with persistently high G-protein activity in rod ON bipolar cell dendrites caused by the absence of the dominant GAP, biasing TRPM1 channels to the closed state.
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.forename: Johan
authors.initials: J
authors.lastname: Pahlberg
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sarria
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamasawa
authors.forename: Alapakkam P
authors.initials: AP
authors.lastname: Sampath
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Martemyanov
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004596:Electroretinography; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D055537:Light Signal Transduction / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000378:metabolism / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020690:GTPase-Activating Proteins; D020710:RGS Proteins; C485693:Rgs11 protein, mouse; C492038:Rgs7 protein, mouse