Regulation of AMPA receptor trafficking by N-cadherin

Mutsuo Nuriya, Richard L. Huganir

Research output: Contribution to journalArticlepeer-review

105 Citations (Scopus)


Dendritic spines are dynamically regulated, both morphologically and functionally, by neuronal activity. Morphological changes are mediated by a variety of synaptic proteins, whereas functional changes can be dramatically modulated by the regulation of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor trafficking. Although these two forms of plasticity appear to be highly coordinated, the connections between them are not fully understood. In this study the synaptic cell adhesion molecule N-cadherin was found to associate with AMPA receptors and regulate AMPA receptor trafficking in neurons. N-cadherin and β-catenin formed a protein complex with AMPA receptors in vivo, and this association was regulated by extracellular Ca2+. In addition, these proteins co-clustered at synapses in cultured neurons. In heterologous cells and in cultured neurons, overexpression of wild-type N-cadherin specifically increased the surface expression level of the AMPA receptor subunit glutamate receptor 1 (GluR1)q4 and this effect was reversed by a dominant-negative form of N-cadherin. Finally, GluR1 increased the surface expression of N-cadherin in heterologous cells. Importantly, recent studies suggest that N-cadherin and β-catenin play key roles in structural plasticity in neurons. Therefore, our data suggest that the association of N-cadherin with AMPA receptors may serve as a biochemical link between structural and functional plasticity of synapses.

Original languageEnglish
Pages (from-to)652-661
Number of pages10
JournalJournal of Neurochemistry
Issue number3
Publication statusPublished - 2006 May
Externally publishedYes


  • Excitatory synapses
  • Glutamate
  • N-cadherin
  • Spine
  • Trafficking
  • α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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