The glutamate receptor-interacting protein family of GluR2-binding proteins is required for long-term synaptic depression expression in cerebellar Purkinje cells

Kogo Takamiya, Lifang Mao, Richard L. Huganir, David J. Linden

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Glutamate receptor-interacting protein 1 (GRIP1) and GRIP2 are closely related proteins that bind GluR2-containing AMPA receptors and couple them to structural and signaling complexes in neurons. Cerebellar long-term synaptic depression (LTD) is a model system of synaptic plasticity that is expressed by persistent internalization of GluR2-containing AMPA receptors. Here, we show that genetic deletion of both GRIP1 and GRIP2 blocks LTD expression in primary cultures of mouse cerebellar neurons but that single deletion of either isoform allows LTD to occur. In GRIP1/2 double knock-out Purkinje cells, LTD can be fully rescued by a plasmid-driving expression of GRIP1 and partially rescued by a GRIP2 plasmid. These results indicate that the GRIP family comprises an essential molecular component for cerebellar LTD.

Original languageEnglish (US)
Pages (from-to)5752-5755
Number of pages4
JournalJournal of Neuroscience
Volume28
Issue number22
DOIs
StatePublished - May 28 2008

Keywords

  • AMPA receptor
  • Cerebellum
  • Dendrite
  • Glutamate
  • Motor learning
  • Plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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