Protein kinase D promotes activity-dependent AMPA receptor endocytosis in hippocampal neurons

Traffic. 2021 Dec;22(12):454-470. doi: 10.1111/tra.12819. Epub 2021 Oct 5.


α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptors (AMPARs) mediate the majority of fast excitatory neurotransmission in the brain. The continuous trafficking of AMPARs into and out of synapses is a core feature of synaptic plasticity, which is considered as the cellular basis of learning and memory. The molecular mechanisms underlying the postsynaptic AMPAR trafficking, however, are still not fully understood. In this work, we demonstrate that the protein kinase D (PKD) family promotes basal and activity-induced AMPAR endocytosis in primary hippocampal neurons. Pharmacological inhibition of PKD increased synaptic levels of GluA1-containing AMPARs, slowed down their endocytic trafficking and increased neuronal network activity. By contrast, ectopic expression of constitutive active PKD decreased the synaptic level of AMPARs, while increasing their colocalization with early endosomes. Our results thus establish an important role for PKD in the regulation of postsynaptic AMPAR trafficking during synaptic plasticity.

Keywords: AMPA receptor; GluA1; PKD; chemically induced LTD; endocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endocytosis / physiology
  • Hippocampus* / metabolism
  • Neuronal Plasticity / physiology
  • Neurons / metabolism
  • Protein Kinase C
  • Receptors, AMPA* / metabolism
  • Synapses / metabolism


  • Receptors, AMPA
  • protein kinase D
  • Protein Kinase C