The Brain and Mind Research Institute and The Centre for Mathematical Biology, The University of Sydney, Sydney, New South Wales, 2006, Australia.
Bull Math Biol. 2012 Mar;74(3):717-35. doi: 10.1007/s11538-011-9706-9. Epub 2011 Dec 7.
Neuregulin (Nrg) through its receptor ErbB4 modulates the activity of the N-Methyl-D-Aspartate (NMDA) receptor (NMDAR) at synapses. As modification of this pathway has been implicated in schizophrenia, it is of great interest to define it in precise quantitative terms. Kinetic models of the epidermal growth factor (EGF)/ErbB receptor signalling pathway describing activation, desensitization, and tyrosine phosphorylation of EGFR/ErbB followed by binding and activation of Src family kinases that is subsequently followed by phosphorylation of target proteins are available. We have adapted these to give a kinetic description of NMDAR modulation by Nrg that recapitulates the observed kinetics of autophosphorylation of the ErbB dimer as well as the modulation of the NMDAR by Src kinase, according to whether the kinases are activated or deactivated. This quantitative description of the Nrg/NMDAR pathway provides a model for experimental elucidation of what goes awry in animal models of schizophrenia.
神经调节蛋白 (Nrg) 通过其受体 ErbB4 调节突触处 N-甲基-D-天冬氨酸 (NMDA) 受体 (NMDAR) 的活性。由于该途径的修饰与精神分裂症有关，因此以精确的定量术语来定义它非常重要。描述表皮生长因子 (EGF)/ErbB 受体信号通路激活、脱敏和酪氨酸磷酸化的 EGF/ErbB 的 EGFR/ErbB 动力学模型，随后是Src 家族激酶的结合和激活，随后是靶蛋白的磷酸化，这些模型都可用。我们已经对其进行了改编，以提供 Nrg 对 NMDAR 调节的动力学描述，该描述再现了观察到的 ErbB 二聚体自身磷酸化的动力学，以及根据激酶是激活还是失活，Src 激酶对 NMDAR 的调节。该 Nrg/NMDAR 通路的定量描述为精神分裂症动物模型中出现问题的实验阐明提供了模型。
