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Keywords:

  • actin;
  • calpain;
  • clustering;
  • internalization;
  • parallel fibre

Abstract

The δ2 glutamate receptor (δ2 receptor), which is expressed abundantly at parallel fibre–Purkinje neuron synapses, has an important role in synaptogenesis and synaptic plasticity in the cerebellum. The present study examined the molecular mechanisms regulating synaptic δ2 receptor density. Immunocytochemistry, using two antibodies against the intracellular C-terminal and extracellular N-terminal regions of the δ2 receptor, indicated the reversible redistribution of postsynaptic δ2 receptors in response to either glutamatergic stimulation or enhancement of synaptic activity. The effect of glutamatergic stimulation was completely inhibited by either coapplication of the glutamate receptor antagonist or the removal of extracellular Ca2+ using EGTA and mimicked by selective activation of voltage-gated Ca2+ channels (VGCCs) with KCl, suggesting the significant role of Ca2+ influx in δ2 receptor redistribution. Biochemical examination indicated that a large amount of δ2 receptor protein was internalized following glutamatergic stimulation. These results suggest that the number of synaptic δ2 receptors is controlled by endocytosis in a synaptic activity- and intracellular Ca2+-dependent way, through which synaptogenesis and synaptic plasticity in Purkinje cells might be modulated.