alpha-Actinin Anchors PSD-95 at Postsynaptic Sites

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Matt L., Kim K., Hergarden A. C., Patriarchi T., Malik Z. A., Park D. K., ...More

NEURON, vol.97, no.5, pp.1094-1118, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 97 Issue: 5
  • Publication Date: 2018
  • Doi Number: 10.1016/j.neuron.2018.01.036
  • Journal Name: NEURON
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1094-1118
  • Akdeniz University Affiliated: Yes

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 alpha-actinin binds to the very N terminus of PSD-95. Knockdown (KD) of alpha-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 alpha-actinin, respectively, to lysine impairs, in parallel, PSD-95 binding to alpha-actinin and postsynaptic localization of PSD-95 and AMPARs. These experiments identify alpha-actinin as a critical PSD-95 anchor tethering the AMPAR-PSD-95 complex to postsynaptic sites.