AMPA receptor trafficking and Synaptic plasticity require SQSTM1/p62

Jianxiong Jiang, Kodeeswaran Parameshwaran, M. Lamar Seibenhener, Myoung Goo Kang, Vishnu Suppiramaniam, Richard L. Huganir, Maria T. Diaz-Meco, Marie W. Wooten

Research output: Contribution to journalArticlepeer-review

Abstract

SQSTM1/p62 is a multidomain/scaffold for the atypical protein kinase Cs (aPKC). Phosphorylation of AMPA receptors by PKC has been shown to regulate their insertion in the postsynaptic membrane. Here, we directly tested whether p62 could interact with AMPA receptor subynits and influence their trafficking and phosphorylation. GluRI receptor intracellular loop L2-3 and the ZZ-type zinc finger domain of p62 are essential for the interaction between these two proteins. In this context, both p62 and aPKC-mediated phosphorylation were necessary for surface delivery of the receptor. Our findings reveal that p62 is the first protein identified that interacts with a region of the CluR receptor other than the C-terminal tail. Furthermore, mice deficient in p62 displayed impaired hippocampal CA1 long-term potentiation (LTP), along with diminished surface expression of GluRI and phosphorylation of S818. Lastly, we identify a conserved sequence (ISExSL) shared by all p62 interacting-aPKC substrates. These findings support a model where p62 interaction and aPKC phosphorylation act together to mediate AMPA receptor trafficking and long-term synaptic plasticity in the hippocampus.

Original languageEnglish (US)
Pages (from-to)392-406
Number of pages15
JournalHippocampus
Volume19
Issue number4
DOIs
StatePublished - Apr 2009

Keywords

  • GluR1
  • LTP
  • Phosphorylation
  • Surface delivery
  • aPKC

ASJC Scopus subject areas

  • Cognitive Neuroscience

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