Functional redundancy of R7 RGS proteins in ON-bipolar cell dendrites.
OBJECTIVE
In the Gbeta5(-/-) mouse, the electroretinogram (ERG) b-wave is absent, and the R7 subfamily of regulators of G protein signaling (RGS), which includes RGS6, -7, -9, and -11, is downregulated. Mutant mouse strains deficient in RGS7 or -11 were characterized, and the SG711 strain which is deficient in both proteins was examined, to learn whether the loss of some of these RGS proteins causes the absence of the ERG b-wave.


METHODS
Antibodies to RGS7 and -11 were generated to determine their expression levels and localizations in retinas with various genetic backgrounds by Western blot analysis and immunohistochemistry, respectively. The implicit times and amplitudes of ERG a- and b-waves were analyzed to examine photoreceptor and bipolar cell functions.


RESULTS
RGS7 and -11 co-localized to the dendritic tips of the ON-bipolar cells. In the RGS11(-/-) mouse, the level of RGS7 protein increased. However, the level of RGS11 protein remained unchanged in the RGS7 mutant mouse, where a truncated RGS7 protein was expressed due to the deletion of exon 10. In the SG711 mouse retina, the Gbeta5-S protein level was reduced. The ERG b-wave of SG711 mice was markedly delayed. In contrast, RGS11(-/-) mice showed a moderately delayed b-wave, whereas the RGS7 mutant mice showed normal ERG responses.


CONCLUSIONS
The data demonstrate the presence of a delayed ERG b-wave in SG711 mice and a functionally redundant role for RGS11 and -7 at the tips of ON-bipolar cell dendrites. These results suggest that RGS11 or -7 works as the major physiological GAP (GTPase acceleration protein) for Galphao1 in ON-bipolar cells.
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Frank S
FS
Chen
Hoon
H
Shim
Duncan
D
Morhardt
Rebecca
R
Dallman
Elizabeth
E
Krahn
Ludine
L
McWhinney
Anjali
A
Rao
Stephen J
SJ
Gold
Ching-Kang
CK
Chen
D000818:Animals; D015153:Blotting, Western; D003712:Dendrites / Q000502:physiology*; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010775:Photic Stimulation; D020710:RGS Proteins / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014785:Vision, Ocular / Q000502:physiology
D044387:GTP-Binding Protein beta Subunits; D020690:GTPase-Activating Proteins; C094668:Gnb5 protein, mouse; D020710:RGS Proteins; C485693:Rgs11 protein, mouse; C492038:Rgs7 protein, mouse