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Lack of mG luR6‐related cascade elements leads to retrograde trans‐synaptic effects on rod photoreceptor synapses via matrix‐associated proteins
Author(s) -
Tummala Shanti R.,
Dhingra Anuradha,
Fina Marie E.,
Li Jian J.,
Ramakrishnan Hariharasubramanian,
Vardi Noga
Publication year - 2016
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13243
Subject(s) - heterotrimeric g protein , microbiology and biotechnology , chemistry , g protein , metabotropic receptor , signal transduction , biology , receptor , biochemistry , glutamate receptor
Heterotrimeric G‐proteins couple metabotropic receptors to downstream effectors. In retinal ON bipolar cells, G o couples the metabotropic receptor mG luR6 to the TRPM 1 channel and closes it in the dark, thus hyperpolarizing the cell. Light, via GTP ase‐activating proteins, deactivates G o , opens TRPM 1 and depolarizes the cell. G o comprises Gα o1 , Gβ3 and Gγ13; all are necessary for efficient coupling. In addition, Gβ3 contributes to trafficking of certain cascade proteins and to maintaining the synaptic structure. The goal of this study was to determine the role of Gα o1 in maintaining the cascade and synaptic integrity. Using mice lacking Gα o1 , we quantified the immunostaining of certain mG luR6‐related components. Deleting Gα o1 greatly reduced staining for Gβ3, Gγ13, Gβ5, RGS 11, RGS 7 and R9 AP . Deletion of Gα o1 did not affect mG luR6, TRPM 1 or PCP 2. In addition, deleting Gα o1 reduced the number of rod bipolar dendrites that invaginate the rod terminal, similar to the effect seen in the absence of mG luR6, Gβ3 or the matrix‐associated proteins, pikachurin, dystroglycan and dystrophin, which are localized presynaptically to the rod bipolar cell. We therefore tested mice lacking mG luR6, Gα o1 and Gβ3 for expression of these matrix‐associated proteins. In all three genotypes, staining intensity for these proteins was lower than in wild type, suggesting a retrograde trans‐synaptic effect. We propose that the mG luR6 macromolecular complex is connected to the presynaptic rod terminal via a protein chain that includes the matrix‐associated proteins. When a component of the macromolecular chain is missing, the chain may fall apart and loosen the dendritic tip adherence within the invagination.