Brain-derived neurotrophic factor rapidly increases NMDA receptor channel activity through Fyn-mediated phosphorylation.
Brain-derived neurotrophic factor (BDNF) is a potent modulator of hippocampal synaptic plasticity. Previously, we found that one of the targets of BDNF modulation is NR2B-containing NMDA receptors. Furthermore, exposure to the trophin rapidly increases NMDA receptor activity and enhances tyrosine phosphorylation of NR2B in cortical and hippocampal postsynaptic densities (PSDs), potentially linking receptor phosphorylation to synaptic plasticity. To define the specific NR2B residue(s) regulated by BDNF, we focused on tyrosine 1472, phosphorylation of which increases after LTP. BDNF rapidly increased phosphorylation in cortical PSDs. The tyrosine kinase Fyn is critical since BDNF-dependent phosphorylation was abolished in Fyn knockout mice. Single-channel patch clamp recordings showed that Fyn is required for the increase in NMDA receptor activity elicited by BDNF. Collectively, our results suggest that BDNF enhances phosphorylation of NR2B tyrosine 1472 through activation of Fyn, leading to alteration of NMDA receptor activity and increased synaptic transmission.
Xu
Fei
F
Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Plummer
Mark R
MR
Len
Guo-Wei
GW
Nakazawa
Takanobu
T
Yamamoto
Tadashi
T
Black
Ira B
IB
Wu
Kuo
K
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D019000:Phosphotyrosine; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn