Extracellular interactions between GluR2 and N-cadherin in spine regulation

Neuron. 2007 May 3;54(3):461-77. doi: 10.1016/j.neuron.2007.04.012.


Via its extracellular N-terminal domain (NTD), the AMPA receptor subunit GluR2 promotes the formation and growth of dendritic spines in cultured hippocampal neurons. Here we show that the first N-terminal 92 amino acids of the extracellular domain are necessary and sufficient for GluR2's spine-promoting activity. Moreover, overexpression of this extracellular domain increases the frequency of miniature excitatory postsynaptic currents (mEPSCs). Biochemically, the NTD of GluR2 can interact directly with the cell adhesion molecule N-cadherin, in cis or in trans. N-cadherin-coated beads recruit GluR2 on the surface of hippocampal neurons, and N-cadherin immobilization decreases GluR2 lateral diffusion on the neuronal surface. RNAi knockdown of N-cadherin prevents the enhancing effect of GluR2 on spine morphogenesis and mEPSC frequency. Our data indicate that in hippocampal neurons N-cadherin and GluR2 form a synaptic complex that stimulates presynaptic development and function as well as promoting dendritic spine formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Cells, Cultured
  • Embryo, Mammalian
  • Excitatory Postsynaptic Potentials / physiology
  • Extracellular Space / metabolism*
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology
  • Mutation
  • Nerve Tissue Proteins / metabolism
  • Neurons / ultrastructure
  • Patch-Clamp Techniques / methods
  • Protein Structure, Tertiary / physiology
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • RNA Interference / physiology
  • Rats
  • Receptors, AMPA / metabolism*
  • Spine / metabolism*
  • Transfection / methods


  • Cadherins
  • Nerve Tissue Proteins
  • Receptors, AMPA
  • Green Fluorescent Proteins
  • glutamate receptor ionotropic, AMPA 2