Neuregulin1 (NRG1) Signaling through Fyn Modulates NMDA Receptor Phosphorylation: Differential Synaptic Function in NRG1+/− Knock-Outs Compared with Wild-Type Mice
作者： M. Bjarnadottir , D. L. Misner , S. Haverfield-Gross , S. Bruun , V. G. Helgason
DOI: 10.1523/JNEUROSCI.4314-06.2007
关键词: NMDA receptor 、 Tyrosine kinase 、 Phosphorylation 、 Synaptic plasticity 、 Tyrosine kinase 2 、 ERBB4 、 Biology 、 FYN 、 Cancer research 、 Receptor tyrosine kinase 、 Cell biology
摘要: We previously identified Neuregulin1 ( NRG1 ) as a gene contributing to the risk of developing schizophrenia. Furthermore, we showed that +/− mutant mice display behavioral abnormalities are reversed by clozapine, an atypical antipsychotic drug used for treatment now present evidence ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4), tyrosine kinase receptor in hippocampal neurons, interacts with two nonreceptor kinases, Fyn and Pyk2 (proline-rich 2). stimulation cells expressing leads association consequent activation. show signaling, through activation stimulates phosphorylation Y1472 on NR2B subunit NMDA (NMDAR), key regulatory site modulates channel properties. is hypophosphorylated mice, this defect can be clozapine at dose reverses their abnormalities. also demonstrate short-term synaptic plasticity altered theta-burst long-term potentiation impaired incubation slices from these those effects. Attenuated signaling may contribute pathophysiology schizophrenia dysfunction NMDAR modulation. Thus, our data support glutamate hypothesis
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