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J Neurosci. 2012 Aug 15;32(33):11343-55. doi: 10.1523/JNEUROSCI.1436-12.2012.

Gβ3 is required for normal light ON responses and synaptic maintenance.

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Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.


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.

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