Kinase-independent requirement of EphB2 receptors in hippocampal synaptic plasticity.
During development, Eph receptors mediate the repulsive axon guidance function of ephrins, a family of membrane attached ligands with their own receptor-like signaling potential. In cultured glutamatergic neurons, EphB2 receptors were recently shown to associate with NMDA receptors at synaptic sites and were suggested to play a role in synaptogenesis. Here we show that Eph receptor stimulation in cultured neurons modulates signaling pathways implicated in synaptic plasticity, suggesting cross-talk with NMDA receptor-activated pathways. Mice lacking EphB2 have normal hippocampal synapse morphology, but display defects in synaptic plasticity. In EphB2(-/-) hippocampal slices, protein synthesis-dependent long-term potentiation (LTP) was impaired, and two forms of synaptic depression were completely extinguished. Interestingly, targeted expression of a carboxy-terminally truncated form of EphB2 rescued the EphB2 null phenotype, indicating that EphB2 kinase signaling is not required for these EphB2-mediated functions.
Grunwald
I C
IC
Department of Molecular Neurobiology, Max-Planck-Institute of Neurobiology, Am Klopferspitz 18a, D-82152, Martinsried, Germany.
Korte
M
M
Wolfer
D
D
Wilkinson
G A
GA
Unsicker
K
K
Lipp
H P
HP
Bonhoeffer
T
T
Klein
R
R
D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004594:Electrophysiology; D036387:Ephrin-B1; D036389:Ephrin-B3; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D007763:Lac Operon; D008024:Ligands; D017774:Long-Term Potentiation / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D036183:Receptor, EphB2; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology; D001616:beta-Galactosidase / Q000235:genetics
D036387:Ephrin-B1; D036389:Ephrin-B3; D008024:Ligands; D008565:Membrane Proteins; C409466:NR1 NMDA receptor; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D011494:Protein Kinases; D020794:Receptor Protein-Tyrosine Kinases; D036183:Receptor, EphB2; D001616:beta-Galactosidase