AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions

Watson J, Pinggera A, Ho H, Greger IH. 2021. AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. 12(1), 5083.

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Author
Watson, JakeIST Austria ; Pinggera, Alexandra; Ho, Hinze; Greger, Ingo H.
Department
Abstract
AMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates the strength of transmission. Changes in AMPAR localisation can enact synaptic plasticity, allowing long-term information storage, and is therefore tightly controlled. Multiple mechanisms regulating AMPAR synaptic anchoring have been described, but with limited coherence or comparison between reports, our understanding of this process is unclear. Here, combining synaptic recordings from mouse hippocampal slices and super-resolution imaging in dissociated cultures, we compare the contributions of three AMPAR interaction domains controlling transmission at hippocampal CA1 synapses. We show that the AMPAR C-termini play only a modulatory role, whereas the extracellular N-terminal domain (NTD) and PDZ interactions of the auxiliary subunit TARP γ8 are both crucial, and each is sufficient to maintain transmission. Our data support a model in which γ8 accumulates AMPARs at the postsynaptic density, where the NTD further tunes their positioning. This interplay between cytosolic (TARP γ8) and synaptic cleft (NTD) interactions provides versatility to regulate synaptic transmission and plasticity.
Publishing Year
Date Published
2021-08-23
Journal Title
Nature Communications
Acknowledgement
The authors are very grateful to Andrew Penn for advice and discussions on surface receptor labelling in slice tissue, dissociated culture transfection, and for providing tdTomato and BirAER expression plasmids. This work would not have been possible without support from the Biological Services teams at both the Laboratory of Molecular Biology and Ares facilities. We are also very grateful to Nick Barry and Jerome Boulanger of the LMB Light Microscopy facility for support with confocal and STORM imaging and analysis, Junichi Takagi for providing scFv-Clasp expression constructs, Veronica Chang for assistance with scFv-Clasp protein production, and Nejc Kejzar for assistance with cluster analysis. We would like to thank Teru Nakagawa and Ole Paulsen for critical reading of the manuscript and constructive feedback. This work was supported by grants from the Medical Research Council (MC_U105174197) and BBSRC (BB/N002113/1).
Volume
12
Issue
1
Article Number
5083
eISSN
IST-REx-ID

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Watson J, Pinggera A, Ho H, Greger IH. AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-25281-4
Watson, J., Pinggera, A., Ho, H., & Greger, I. H. (2021). AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-021-25281-4
Watson, Jake, Alexandra Pinggera, Hinze Ho, and Ingo H. Greger. “AMPA Receptor Anchoring at CA1 Synapses Is Determined by N-Terminal Domain and TARP Γ8 Interactions.” Nature Communications. Nature Publishing Group, 2021. https://doi.org/10.1038/s41467-021-25281-4.
J. Watson, A. Pinggera, H. Ho, and I. H. Greger, “AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions,” Nature Communications, vol. 12, no. 1. Nature Publishing Group, 2021.
Watson J, Pinggera A, Ho H, Greger IH. 2021. AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. 12(1), 5083.
Watson, Jake, et al. “AMPA Receptor Anchoring at CA1 Synapses Is Determined by N-Terminal Domain and TARP Γ8 Interactions.” Nature Communications, vol. 12, no. 1, 5083, Nature Publishing Group, 2021, doi:10.1038/s41467-021-25281-4.
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