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Distribution of the glycine receptor ß-subunit in the mouse CNS as revealed by a novel monoclonal antibody.

Authors: Weltzien, Felix  Puller, Christian  O'Sullivan, Gregory A  Paarmann, Ingo  Betz, Heinrich 
Citation: Weltzien F, etal., J Comp Neurol. 2012 Dec 1;520(17):3962-81. doi: 10.1002/cne.23139.
Pubmed: (View Article at PubMed) PMID:22592841
DOI: Full-text: DOI:10.1002/cne.23139

Inhibitory glycine receptors (GlyRs) are composed of homologous α- (α1-4) and ß-subunits. The ß-subunits (GlyRß) interact via their large cytosolic loops with the postsynaptic scaffolding protein gephyrin and are therefore considered essential for synaptic localization. In situ hybridization studies indicate a widespread distribution of GlyRß transcripts throughout the mammalian central nervous system (CNS), whereas GlyRα mRNAs and proteins display more restricted expression patterns. Here we report the generation of a monoclonal antibody that specifically recognizes rodent GlyRß (mAb-GlyRß) and does not exhibit crossreactivity with any of the GlyRα1-4 subunits. Immunostaining with this antibody revealed high densities of punctate GlyRß immunoreactivity at inhibitory synapses in mouse spinal cord, brainstem, midbrain, and olfactory bulb but not in the neocortex, cerebellum, or hippocampus. This contrasts the abundance of GlyRß transcripts in all major regions of the rodent brain and suggests that GlyRß protein levels are regulated posttranscriptionally. When mAb-GlyRß was used in double-labeling experiments with GlyRα1-, α2-, α3-, or α4-specific antibodies to examine the colocalization of GlyRß with these GlyR subunits in the mouse retina, >90% of the GlyRα1-3 clusters detected were found to be GlyRß-immunoreactive. A subset (about 50%) of the GlyRα4 puncta in the inner plexiform layer, however, was found to lack GlyRß and gephyrin immunostaining. These GlyRα4-only clusters were apposed to bassoon immunoreactivity and hence synaptically localized. Their existence points to a gephyrin-independent synaptic localization mechanism for a minor subset of GlyRs.

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RGD Object Information
RGD ID: 13702311
Created: 2018-07-18
Species: All species
Last Modified: 2018-07-18
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.