The receptor tyrosine kinase EphB2 regulates NMDA-dependent synaptic function

Neuron. 2001 Dec 20;32(6):1041-56. doi: 10.1016/s0896-6273(01)00553-0.

Abstract

Members of the Eph family of receptor tyrosine kinases control many aspects of cellular interactions during development, including axon guidance. Here, we demonstrate that EphB2 also regulates postnatal synaptic function in the mammalian CNS. Mice lacking the EphB2 intracellular kinase domain showed wild-type levels of LTP, whereas mice lacking the entire EphB2 receptor had reduced LTP at hippocampal CA1 and dentate gyrus synapses. Synaptic NMDA-mediated current was reduced in dentate granule neurons in EphB2 null mice, as was synaptically localized NR1 as revealed by immunogold localization. Finally, we show that EphB2 is upregulated in hippocampal pyramidal neurons in vitro and in vivo by stimuli known to induce changes in synaptic structure. Together, these data demonstrate that EphB2 plays an important role in regulating synaptic function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dentate Gyrus / cytology
  • Dentate Gyrus / physiology
  • Ephrin-B2
  • Excitatory Amino Acid Agonists / pharmacology
  • Gene Expression Regulation, Developmental / physiology
  • Glutamic Acid / metabolism
  • In Vitro Techniques
  • Kainic Acid / pharmacology
  • Long-Term Potentiation / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Neuronal Plasticity / physiology
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, EphB2
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Ephrin-B2
  • Excitatory Amino Acid Agonists
  • Membrane Proteins
  • NMDA receptor A1
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Receptor Protein-Tyrosine Kinases
  • Receptor, EphB2
  • Kainic Acid