Activity-dependent endocytic sorting of kainate receptors to recycling or degradation pathways

EMBO J. 2004 Dec 8;23(24):4749-59. doi: 10.1038/sj.emboj.7600483. Epub 2004 Nov 18.


Kainate receptors (KARs) play important roles in the modulation of neurotransmission and plasticity, but the mechanisms that regulate their surface expression and endocytic sorting remain largely unknown. Here, we show that in cultured hippocampal neurons the surface expression of GluR6-containing KARs is dynamically regulated. Furthermore, internalized KARs are sorted into recycling or degradative pathways depending on the endocytotic stimulus. Kainate activation causes a Ca2+- and PKA-independent but PKC-dependent internalization of KARs that are targeted to lysosomes for degradation. In contrast, NMDAR activation evokes a Ca2+-, PKA- and PKC-dependent endocytosis of KARs to early endosomes with subsequent reinsertion back into the plasma membrane. These results demonstrate that GluR6-containing KARs are subject to activity-dependent endocytic sorting, a process that provides a mechanism for both rapid and chronic changes in the number of functional receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bicuculline / pharmacology
  • Calcium / metabolism
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Endocytosis / physiology*
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / pharmacology
  • Hippocampus / cytology
  • Kainic Acid / pharmacology
  • Lysosomes / metabolism
  • N-Methylaspartate / pharmacology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Protein Subunits / metabolism*
  • Protein Transport*
  • Receptors, Kainic Acid / metabolism*
  • Tetrodotoxin / pharmacology


  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Gluk2 kainate receptor
  • Protein Subunits
  • Receptors, Kainic Acid
  • Tetrodotoxin
  • N-Methylaspartate
  • Cyclic AMP-Dependent Protein Kinases
  • Kainic Acid
  • Calcium
  • Bicuculline