Brain-derived neurotrophic factor rapidly increases NMDA receptor channel activity through Fyn-mediated phosphorylation.

Xu, Fei; Plummer, Mark R; Len, Guo-Wei; Nakazawa, Takanobu; Yamamoto, Tadashi; Black, Ira B; Wu, Kuo

Xu, Fei; Plummer, Mark R; Len, Guo-Wei; Nakazawa, Takanobu; Yamamoto, Tadashi; Black, Ira B; Wu, Kuo.

Afiliación

Xu F; Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.

Brain Res ; 1121(1): 22-34, 2006 Nov 22.

Article en En | MEDLINE | ID: mdl-17045972

RESUMEN

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.

Asunto(s)

Factor Neurotrófico Derivado del Encéfalo/farmacología; Neuronas/fisiología; Proteínas Proto-Oncogénicas c-fyn/fisiología; Receptores de N-Metil-D-Aspartato/fisiología; Animales; Técnicas de Cultivo de Célula; Corteza Cerebral/efectos de los fármacos; Corteza Cerebral/fisiología; Hipocampo/citología; Hipocampo/embriología; Hipocampo/fisiología; Ratones; Ratones Noqueados; Neuronas/efectos de los fármacos; Fosforilación; Fosfotirosina/metabolismo; Proteínas Proto-Oncogénicas c-fyn/deficiencia; Proteínas Proto-Oncogénicas c-fyn/genética; Ratas; Ratas Sprague-Dawley; Receptores de N-Metil-D-Aspartato/efectos de los fármacos

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de N-Metil-D-Aspartato / Factor Neurotrófico Derivado del Encéfalo / Proteínas Proto-Oncogénicas c-fyn / Neuronas Límite: Animals Idioma: En Revista: Brain Res Año: 2006 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links