α-Actinin Anchors PSD-95 at Postsynaptic Sites

Neuron. 2018 Mar 7;97(5):1094-1109.e9. doi: 10.1016/j.neuron.2018.01.036. Epub 2018 Feb 8.

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.

Keywords: AMPA receptors; PSD-95; dendritic spines; hippocampus; synapse; α-actinin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin / chemistry
  • Actinin / genetics
  • Actinin / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Disks Large Homolog 4 Protein / chemistry
  • Disks Large Homolog 4 Protein / genetics
  • Disks Large Homolog 4 Protein / metabolism*
  • Excitatory Postsynaptic Potentials / physiology*
  • Female
  • HEK293 Cells
  • Hippocampus / metabolism*
  • Humans
  • Male
  • Protein Structure, Secondary
  • Rats

Substances

  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Actinin