The receptor tyrosine kinase EphB2 regulates NMDA-dependent synaptic function.
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.
Henderson
J T
JT
Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Toronto, Ontario, Canada. henderson@mshri.on.ca
Georgiou
J
J
Jia
Z
Z
Robertson
J
J
Elowe
S
S
Roder
J C
JC
Pawson
T
T
D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology; D036388:Ephrin-B2; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009473:Neuronal Plasticity / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D036183:Receptor, EphB2; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D036388:Ephrin-B2; D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D007608:Kainic Acid; D008565:Membrane Proteins; D020794:Receptor Protein-Tyrosine Kinases; D036183:Receptor, EphB2; D016194:Receptors, N-Methyl-D-Aspartate