Retina-specific GTPase accelerator RGS11/G beta 5S/R9AP is a constitutive heterotrimer selectively targeted to mGluR6 in ON-bipolar neurons.
Members of the R7 family of the regulators of G-protein signaling (R7 RGS) proteins form multi-subunit complexes that play crucial roles in processing the light responses of retinal neurons. The disruption of these complexes has been shown to lead to the loss of temporal resolution in retinal photoreceptors and deficient synaptic transmission to downstream neurons. Despite the well established role of one member of this family, RGS9-1, in controlling vertebrate phototransduction, the roles and organizational principles of other members in the retina are poorly understood. Here we investigate the composition, localization, and function of complexes containing RGS11, the closest homolog of RGS9-1. We find that RGS11 forms a novel obligatory trimeric complex with the short splice isoform of the type 5 G-protein beta subunit (G beta 5) and the RGS9 anchor protein (R9AP). The complex is expressed exclusively in the dendritic tips of ON-bipolar cells in which its localization is accomplished through a direct association with mGluR6, the glutamate receptor essential for the ON-bipolar light response. Although association with both R9AP and mGluR6 contributed to the proteolytic stabilization of the complex, postsynaptic targeting of RGS11 was not determined by its membrane anchor R9AP. Electrophysiological recordings of the light response in mouse rod ON-bipolar cells reveal that the genetic elimination of RGS11 has little effect on the deactivation of G alpha(o) in dark-adapted cells or during adaptation to background light. These results suggest that the deactivation of mGluR6 cascade during the light response may require the contribution of multiple GTPase activating proteins.
Cao
Yan
Y
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Masuho
Ikuo
I
Okawa
Haruhisa
H
Xie
Keqiang
K
Asami
Junko
J
Kammermeier
Paul J
PJ
Maddox
Dennis M
DM
Furukawa
Takahisa
T
Inoue
Takayoshi
T
Sampath
Alapakkam P
AP
Martemyanov
Kirill A
KA
D000818:Animals; D002460:Cell Line; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008027:Light; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology / Q000648:ultrastructure; D020033:Protein Isoforms / Q000378:metabolism; D055503:Protein Multimerization; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000502:physiology / Q000648:ultrastructure; D051245:Retinal Bipolar Cells / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure
D044387:GTP-Binding Protein beta Subunits; C094668:Gnb5 protein, mouse; D008565:Membrane Proteins; D020033:Protein Isoforms; C508769:R9AP protein, mouse; D020710:RGS Proteins; D018094:Receptors, Metabotropic Glutamate; C485693:Rgs11 protein, mouse; C113897:metabotropic glutamate receptor 6