α-Actinin Anchors PSD-95 at Postsynaptic Sites

Lucas Matt, Karam Kim, Anne C. Hergarden, Tommaso Patriarchi, Zulfiqar A. Malik, Deborah K. Park, Dhrubajyoti Chowdhury, Olivia R. Buonarati, Peter B. Henderson, Çiğdem Gökçek Saraç, Yonghong Zhang, Durga Mohapatra, Mary C. Horne, James B. Ames, Johannes W. Hell

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Despite the central role PSD-95 plays in anchoring postsynaptic AMPARs, how PSD-95 itself is tethered to postsynaptic sites is not well understood. Here we show that the F-actin binding protein α-actinin binds to the very N terminus of PSD-95. Knockdown (KD) of α-actinin phenocopies KD of PSD-95. Mutating lysine at position 10 or lysine at position 11 of PSD-95 to glutamate, or glutamate at position 53 or glutamate and aspartate at positions 213 and 217 of α-actinin, respectively, to lysine impairs, in parallel, PSD-95 binding to α-actinin and postsynaptic localization of PSD-95 and AMPARs. These experiments identify α-actinin as a critical PSD-95 anchor tethering the AMPAR-PSD-95 complex to postsynaptic sites. Matt et al. introduce α-actinin as a critical postsynaptic docking protein for PSD-95 and AMPARs. They found that disruption of the PSD-95-α-actinin interaction by point-mutating the essential residues on either protein leads to reduced synaptic localization of PSD-95 and AMPARs.

Original languageEnglish
Pages (from-to)1094-1109.e9
JournalNeuron
Volume97
Issue number5
DOIs
StatePublished - Mar 7 2018

Keywords

  • AMPA receptors
  • PSD-95
  • dendritic spines
  • hippocampus
  • synapse
  • α-actinin

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    Matt, L., Kim, K., Hergarden, A. C., Patriarchi, T., Malik, Z. A., Park, D. K., Chowdhury, D., Buonarati, O. R., Henderson, P. B., Gökçek Saraç, Ç., Zhang, Y., Mohapatra, D., Horne, M. C., Ames, J. B., & Hell, J. W. (2018). α-Actinin Anchors PSD-95 at Postsynaptic Sites. Neuron, 97(5), 1094-1109.e9. https://doi.org/10.1016/j.neuron.2018.01.036