Gβ3 is required for normal light ON responses and synaptic maintenance.
Heterotrimeric G-proteins, comprising Gα and Gβγ subunits, couple metabotropic receptors to various downstream effectors and contribute to assembling and trafficking receptor-based signaling complexes. A G-protein β subunit, Gβ(3), plays a critical role in several physiological processes, as a polymorphism in its gene is associated with a risk factor for several disorders. Retinal ON bipolar cells express Gβ(3), and they provide an excellent system to study its role. In the ON bipolar cells, mGluR6 inverts the photoreceptor's signal via a cascade in which glutamate released from photoreceptors closes the TRPM1 channel. This cascade is essential for vision since deficiencies in its proteins lead to complete congenital stationary night blindness. Here we report that Gβ(3) participates in the G-protein heterotrimer that couples mGluR6 to TRPM1. Gβ(3) deletion in mouse greatly reduces the light response under both scotopic and photopic conditions, but it does not eliminate it. In addition, Gβ(3) deletion causes mislocalization and downregulation of most cascade elements and modulators. Furthermore, Gβ(3) may play a role in synaptic maintenance since in its absence, the number of invaginating rod bipolar dendrites is greatly reduced, a deficit that was not observed at 3 weeks, the end of the developmental period.
Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. dhingra@mail.med.upenn.edu
Anuradha
A
Dhingra
Hariharasubramanian
H
Ramakrishnan
Adam
A
Neinstein
Marie E
ME
Fina
Ying
Y
Xu
Jian
J
Li
Daniel C
DC
Chung
Arkady
A
Lyubarsky
Noga
N
Vardi
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003712:Dendrites / Q000648:ultrastructure; D004558:Electric Stimulation; D004596:Electroretinography; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000172:deficiency / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D011422:Propionates / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency / Q000235:genetics; D012160:Retina / Q000166:cytology; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D050053:TRPM Cation Channels / Q000378:metabolism; D014795:Visual Pathways / Q000502:physiology
C114785:2-amino-4-phosphono-propinate; D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011422:Propionates; C508769:R9AP protein, mouse; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D050053:TRPM Cation Channels; C116297:Trpm1 protein, mouse; C113897:metabotropic glutamate receptor 6; D049452:Green Fluorescent Proteins; D002795:Choline O-Acetyltransferase; C524407:GNAT3 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins