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Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, γ-5

Nature Neuroscience volume 12, pages 277–285 (2009)Cite this article

An Erratum to this article was published on 01 June 2009

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Abstract

Although the properties and trafficking of AMPA-type glutamate receptors (AMPARs) depend critically on associated transmembrane AMPAR regulatory proteins (TARPs) such as stargazin (γ-2), no TARP has been described that can specifically regulate the important class of calcium-permeable (CP-) AMPARs. We examined the stargazin-related protein γ-5, which is highly expressed in Bergmann glia, a cell type possessing only CP-AMPARs. γ-5 was previously thought not to be a TARP, and it has been widely used as a negative control. Here we find that, contrary to expectation, γ-5 acts as a TARP and serves this role in Bergmann glia. Whereas γ-5 interacts with all AMPAR subunits, and modifies their behavior to varying extents, its main effect is to regulate the function of AMPAR subunit combinations that lack short-form subunits, which constitute predominantly CP-AMPARs. Our results suggest an important role for γ-5 in regulating the functional contribution of CP-AMPARs.

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Figure 1: γ-5 modifies GluR4 conductance and Po,peak.
Figure 2: γ-5 shows unusual TARP-like features.
Figure 3: γ-5 affects AMPAR rectification.
Figure 4: γ-5 modifies the properties of homomeric GluR1 CP-AMPARs but not those of homomeric GluR6 kainate receptors.
Figure 5: AMPAR responses from BGCs in cerebellar slices suggest a functional role for γ-5.
Figure 6: Evidence for the 'synaptic' activation of γ-5–containing AMPARs in BGCs.
Figure 7: γ-5 differentially affects 'long-form' AMPAR subunits.
Figure 8: γ-5 interacts with short- and long-form AMPAR subunits and affects surface expression.

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  • 16 March 2009

    In the version of this article initially published, the bar graphs in Figure 7c and 7d were misaligned. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank C. Bats and D. Studniarczyk for discussion. AMPAR subunit cDNAs were gifts from S. Heinemann (Salk) and P. Seeburg (Heidelberg). TARP cDNAs (rat; γ-2, γ-3, γ-4, γ-5 and γ-8) were gifts from R. Nicoll (University of California San Francisco). This work was supported by a Wellcome Trust Programme Grant (S.G.C.-C. and M.F.), an MRC Molecular Biology Programme studentship (M.Z.) and a Royal Society-Wolfson Research Award (S.G.C.-C.).

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  1. David Soto and Ian D Coombs: These authors contributed equally to this work.

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  1. Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK

    David Soto, Ian D Coombs, Massimiliano Renzi, Marzieh Zonouzi, Mark Farrant & Stuart G Cull-Candy

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Correspondence to Mark Farrant or Stuart G Cull-Candy.

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Soto, D., Coombs, I., Renzi, M. et al. Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, γ-5. Nat Neurosci 12, 277–285 (2009). https://doi.org/10.1038/nn.2266

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