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Erbin interacts with TARP γ-2 for surface expression of AMPA receptors in cortical interneurons

A Corrigendum to this article was published on 22 November 2013

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Abstract

Inhibitory neurons control the firing of glutamatergic neurons and synchronize brain activity. However, little is known about mechanisms of excitatory synapse formation in inhibitory neurons. Here we demonstrate that Erbin is specifically expressed in cortical inhibitory neurons. It localizes at excitatory synapses and regulates AMPA receptor (AMPAR) surface expression. Erbin mutation reduced mEPSCs and AMPAR currents specifically in parvalbumin (PV)-positive interneurons but not in pyramidal neurons. We found that the AMPAR auxiliary protein TARP γ-2 was specifically expressed in cortical interneurons. Erbin interacts with TARP γ-2 and is crucial for its stability. Deletion of the γ-2–interacting domain in Erbin attenuated surface AMPAR and excitatory transmission in PV-positive interneurons. Furthermore, we observed behavioral deficits in Erbin-null mice and in mice expressing an Erbin truncation mutant that is unable to interact with TARP γ-2. These observations demonstrate a crucial function for Erbin in AMPAR surface expression in cortical PV-positive interneurons and may contribute to a better understanding of psychiatric disorders.

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Figure 1: Erbin is expressed in GABAergic neurons and PV-positive interneurons in neocortex and hippocampus.
Figure 2: Behavioral deficits in Erbin-null mice as compared to wild-type controls.
Figure 3: Erbin is required for excitatory synaptic transmission of PV-positive inhibitory neurons.
Figure 4: Reduced AMPAR surface expression in erbin−/− PV-positive interneurons.
Figure 5: Erbin interaction with γ-2 and regulation of its expression.
Figure 6: Stabilization of γ-2 by Erbin.
Figure 7: Erbin regulation of γ-2 requires the γ-2–interacting domain.
Figure 8: Decreased AMPAR surface expression and mEPSC amplitudes in erbinΔC/ΔC PV-positive interneurons.

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  • 30 July 2013

    In the version of this article initially published, the email address for correspondence was given as lmei@grc.edu. The correct address is lmei@gru.edu. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank S. Tomita (Yale University) and R.A. Nicoll (University of California, San Francisco) for TARP subunit constructs, Y. Yanagawa (National Institute for Physiological Sciences) for Gad-GFP mice, R. Huganir (John Hopkins University) for rabbit polyclonal antibodies to GluA1, GluA2/3 and GluN1, B.-S. Chen (Georgia Regents University) for the GluA1 antibody and A. Terry and K. Bouchard (Georgia Regents University) for assistance on behavioral tests. This work is supported in part by grants from VA Merit Awards and the US National Institutes of Health (NIH) (L.M. and W.-C.X.). L.M. is the Georgia Research Alliance Eminent Scholar in Neuroscience. J.-P.B. is supported by La Ligue Contre le Cancer (Label Ligue 2010). Y.T. is supported by National Nature Sciences foundation of China (NSFC 31271137). T.-M.G. is supported by NSFC 81030022, U1201225.

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Y.T. and L.M. conceived of, designed and directed the project and wrote the manuscript; Y.T. and C.S. conducted biochemical and imaging experiments and analysis; Y.-J.C. conducted electrophysiological experiments and analysis; Y.T. and C.R.B. conducted behavioral analysis; D.L. assisted with imaging experiments and analysis; S.M. and J.-P.B. provided Erbin null mice; Z.L. and T.-M.G. assisted with data interpretation; W.-C.X. helped with data interpretation and provided instruction; L.M. supervised the project.

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Correspondence to Lin Mei.

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Tao, Y., Chen, YJ., Shen, C. et al. Erbin interacts with TARP γ-2 for surface expression of AMPA receptors in cortical interneurons. Nat Neurosci 16, 290–299 (2013). https://doi.org/10.1038/nn.3320

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