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

article AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions published yes Jake Watson author 63836096-4690-11EA-BD4E-32803DDC885E0000-0002-8698-3823 Alexandra Pinggera author Hinze Ho author Ingo H. Greger author PeJo department 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. https://research-explorer.ista.ac.at/download/9985/9991/2021_NatureCommunications_Watson.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Nature Publishing Group2021 eng Nature Communications 2041-1723 34426577 00068767200000610.1038/s41467-021-25281-4 121 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. <a href="https://doi.org/10.1038/s41467-021-25281-4">https://doi.org/10.1038/s41467-021-25281-4</a> 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. J. Watson, A. Pinggera, H. Ho, I.H. Greger, Nature Communications 12 (2021). 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. <a href="https://doi.org/10.1038/s41467-021-25281-4">https://doi.org/10.1038/s41467-021-25281-4</a>. 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:<a href="https://doi.org/10.1038/s41467-021-25281-4">10.1038/s41467-021-25281-4</a> 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:<a href="https://doi.org/10.1038/s41467-021-25281-4">10.1038/s41467-021-25281-4</a>. 99852021-09-05T22:01:23Z2023-08-11T11:07:51Z