PKMζ maintains late long-term potentiation by N-ethylmaleimide- sensitive factor/GluR2-dependent trafficking of postsynaptic AMPA receptors

Yudong Yao, Matthew Taylor Kelly, Sreedharan Sajikumar, Peter Serrano, Dezhi Tian, Peter John Bergold, Julietta Uta Frey, Todd Charlton Sacktor

Research output: Contribution to journalArticle

191 Scopus citations

Abstract

Although the maintenance mechanism of late long-term potentiation (LTP) is critical for the storage of long-term memory, the expression mechanism of synaptic enhancement during late-LTP is unknown. The autonomously active protein kinase C isoform, protein kinase Mζ (PKMζ), is a core molecule maintaining late-LTP. Here we show that PKMζ maintains late-LTP through persistent N-ethylmaleimide-sensitive factor (NSF)/glutamate receptor subunit 2 (GluR2)-dependent trafficking of AMPA receptors (AMPARs) to the synapse. Intracellular perfusion of PKMζ into CA1 pyramidal cells causes potentiation of postsynaptic AMPAR responses; this synaptic enhancement is mediated through NSF/GluR2 interactions but not vesicle-associated membrane protein-dependent exocytosis. PKMζ may act through NSF to release GluR2-containing receptors from a reserve pool held at extrasynaptic sites by protein interacting with C-kinase 1 (PICK1), because disrupting GluR2/PICK1 interactions mimic and occlude PKMζ-mediated AMPAR potentiation. During LTP maintenance, PKMζ directs AMPAR trafficking, as measured by NSF/GluR2-dependent increases of GluR2/3-containing receptors in synaptosomal fractions from tetanized slices. Blocking this trafficking mechanism reverses established late-LTP and persistent potentiation at synapses that have undergone synaptic tagging and capture. Thus, PKMζ maintains late-LTP by persistently modifying NSF/GluR2-dependent AMPAR trafficking to favor receptor insertion into postsynaptic sites.

Original languageEnglish (US)
Pages (from-to)7820-7827
Number of pages8
JournalJournal of Neuroscience
Volume28
Issue number31
DOIs
StatePublished - Jul 30 2008

Keywords

  • GluR2
  • LTP
  • NSF
  • PICK1
  • PKCζ
  • PKMζ

ASJC Scopus subject areas

  • Neuroscience(all)

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