The endosomal protein NEEP21 regulates AMPA receptor-mediated synaptic transmission and plasticity in the hippocampus

Mol Cell Neurosci. 2005 Jun;29(2):313-9. doi: 10.1016/j.mcn.2005.03.011.


The neuron-enriched endosomal protein 21 (NEEP21) has recently been implicated in the regulation of AMPA receptor (AMPAR) trafficking and proposed to participate in the control of synaptic strength. We tested here this possibility at CA3-CA1 synapses in hippocampal slice cultures using antisense-mediated down-regulation of NEEP21 expression or transfection of a fragment of the cytosolic domain of NEEP21. We found that NEEP21 suppression or expression of the dominant-negative fragment reduced spontaneous and evoked AMPAR-mediated synaptic currents without affecting presynaptic properties. The effect specifically resulted from a reduction of currents mediated by AMPA as opposed to NMDA receptors. Blockade of endocytosis, using a peptide interfering with dynamin, revealed a progressive increase of AMPAR responses due to receptor accumulation in control cells, but not following NEEP21 suppression or expression of the fragment. Also, the enhanced receptor cycling induced by bath application of NMDA resulted in a depression that was enhanced following interference with NEEP21 function. Finally, LTP induction, which involves expression of new synaptic receptors, was abolished in NEEP21-depleted cells or cells expressing the dominant-negative fragment. Together, we conclude that NEEP21 contributes to the regulation of synaptic transmission and plasticity in slice cultures by affecting the recycling and targeting of AMPA receptors to the synapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antisense Elements (Genetics)
  • Down-Regulation / physiology
  • Dynamins / antagonists & inhibitors
  • Dynamins / metabolism
  • Endocytosis / drug effects
  • Endocytosis / physiology*
  • Endosomes / drug effects
  • Endosomes / metabolism
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Organ Culture Techniques
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Peptides / pharmacology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Protein Structure, Tertiary / physiology
  • Rats
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Antisense Elements (Genetics)
  • Excitatory Amino Acid Agonists
  • Nerve Tissue Proteins
  • Nsg1 protein, rat
  • Peptide Fragments
  • Peptides
  • Receptors, AMPA
  • Dynamins