Schizophrenia susceptibility pathway neuregulin 1-ErbB4 suppresses Src upregulation of NMDA receptors.
作者： Graham M Pitcher , Lorraine V Kalia , David Ng , Nathalie M Goodfellow , Kathleen T Yee
DOI: 10.1038/NM.2315
关键词:
摘要: Hypofunction of the N-methyl D-aspartate subtype glutamate receptor (NMDAR) is hypothesized to be a mechanism underlying cognitive dysfunction in individuals with schizophrenia. For schizophrenia-linked genes NRG1 and ERBB4, NMDAR hypofunction thus considered key detrimental consequence excessive NRG1-ErbB4 signaling found people However, we show here that neuregulin 1β-ErbB4 (NRG1β-ErbB4) does not cause general NMDARs. Rather, find that, hippocampus prefrontal cortex, NRG1β-ErbB4 suppresses enhancement synaptic currents by nonreceptor tyrosine kinase Src. prevented induction long-term potentiation at hippocampal Schaffer collateral-CA1 synapses suppressed Src-dependent responses during theta-burst stimulation. Moreover, theta burst-induced phosphorylation GluN2B inhibiting Src activity. We propose participates schizophrenia aberrantly suppressing Src-mediated function.
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sci-hub.se 参考文章(60)
Li Ma, Yang Z. Huang, Graham M. Pitcher, Juli G. Valtschanoff, Ying H. Ma, Lin Y. Feng, Bai Lu, Wen C. Xiong, Michael W. Salter, Richard J. Weinberg, Lin Mei, Ligand-dependent recruitment of the ErbB4 signaling complex into neuronal lipid rafts The Journal of Neuroscience. ,vol. 23, pp. 3164- 3175 ,(2003) , 10.1523/JNEUROSCI.23-08-03164.2003
Seth G. N. Grant, Walter P. Blackstock, Proteomics in Neuroscience: From Protein to Network The Journal of Neuroscience. ,vol. 21, pp. 8315- 8318 ,(2001) , 10.1523/JNEUROSCI.21-21-08315.2001
Ryuji Fukazawa, Thomas A Miller, Yukio Kuramochi, Stefan Frantz, Young-Dae Kim, Mark A Marchionni, Ralph A Kelly, Douglas B Sawyer, Neuregulin-1 protects ventricular myocytes from anthracycline-induced apoptosis via erbB4-dependent activation of PI3-kinase/Akt. Journal of Molecular and Cellular Cardiology. ,vol. 35, pp. 1473- 1479 ,(2003) , 10.1016/J.YJMCC.2003.09.012
Michelle A Merrill, Yucui Chen, Stefan Strack, Johannes W Hell, None, Activity-driven postsynaptic translocation of CaMKII. Trends in Pharmacological Sciences. ,vol. 26, pp. 645- 653 ,(2005) , 10.1016/J.TIPS.2005.10.003
Oh-Bin Kwon, Marines Longart, Detlef Vullhorst, Dax A Hoffman, Andres Buonanno, Neuregulin-1 Reverses Long-Term Potentiation at CA1 Hippocampal Synapses Journal of Neuroscience. ,vol. 25, pp. 9378- 9383 ,(2005) , 10.1523/JNEUROSCI.2100-05.2005
Colm M.P. O'Tuathaigh, Anne-Marie O'Connor, Gerard J. O'Sullivan, Donna Lai, Richard Harvey, David T. Croke, John L. Waddington, Disruption to social dyadic interactions but not emotional/anxiety-related behaviour in mice with heterozygous 'knockout' of the schizophrenia risk gene neuregulin-1. Progress in Neuro-psychopharmacology & Biological Psychiatry. ,vol. 32, pp. 462- 466 ,(2008) , 10.1016/J.PNPBP.2007.09.018
Sloka S. Iyengar, David D. Mott, Neuregulin blocks synaptic strengthening after epileptiform activity in the rat hippocampus Brain Research. ,vol. 1208, pp. 67- 73 ,(2008) , 10.1016/J.BRAINRES.2008.02.045
X.-M. Yu, NMDA Channel Regulation by Channel-Associated Protein Tyrosine Kinase Src Science. ,vol. 275, pp. 674- 678 ,(1997) , 10.1126/SCIENCE.275.5300.674
Darrick T. Balu, Joseph T. Coyle, Neuroplasticity Signaling Pathways Linked to the Pathophysiology of Schizophrenia Neuroscience & Biobehavioral Reviews. ,vol. 35, pp. 848- 870 ,(2011) , 10.1016/J.NEUBIOREV.2010.10.005
Zhenglin Gu, Qian Jiang, Amy KY Fu, Nancy Y Ip, Zhen Yan, None, Regulation of NMDA Receptors by Neuregulin Signaling in Prefrontal Cortex The Journal of Neuroscience. ,vol. 25, pp. 4974- 4984 ,(2005) , 10.1523/JNEUROSCI.1086-05.2005