Spatial and Temporal Regulation of Receptor Endocytosis in Neuronal Dendrites Revealed by Imaging of Single Vesicle Formation

Cell Rep. 2017 Feb 21;18(8):1840-1847. doi: 10.1016/j.celrep.2017.01.081.


Endocytosis in neuronal dendrites is known to play a critical role in synaptic transmission and plasticity such as long-term depression (LTD). However, the inability to detect endocytosis directly in living neurons has hampered studies of its dynamics and regulation. Here, we visualized the formation of individual endocytic vesicles containing pHluorin-tagged receptors with high temporal resolution in the dendrites of cultured hippocampal neurons. We show that transferrin receptors (TfRs) are constitutively internalized at optically static clathrin-coated structures. These structures are slightly enriched near synapses that represent preferential sites for the endocytosis of postsynaptic AMPA-type receptors (AMPARs), but not for non-synaptic TfRs. Moreover, the frequency of AMPAR endocytosis events increases after the induction of NMDAR-dependent chemical LTD, but the activity of perisynaptic endocytic zones is not differentially regulated. We conclude that endocytosis is a highly dynamic and stereotyped process that internalizes receptors in precisely localized endocytic zones.

Keywords: AMPA receptor; Beta2 adrenergic receptor; GluA1; GluA2; clathrin-mediated endocytosis; long-term depression; post-synaptic density; transferrin receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Dendrites / metabolism
  • Dendrites / physiology*
  • Endocytosis / physiology*
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Humans
  • Long-Term Potentiation / physiology
  • Long-Term Synaptic Depression / physiology
  • Neuronal Plasticity / physiology
  • Neurons / metabolism
  • Neurons / physiology*
  • Protein Transport / physiology*
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, Transferrin / metabolism
  • Synapses / metabolism
  • Synaptic Transmission / physiology
  • Transport Vesicles / metabolism*


  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Transferrin