Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses
Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses
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DOI：
10.1016/s0896-6273(00)81176-9
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发表时间：
2000-05-01
期刊：
影响因子：
16.2
通讯作者：
Mei, L
中科院分区：
文献类型：
--
作者：
Huang, YZ;Won, S;Mei, L
神经调节蛋白（NRGs）及其受体ErbB蛋白酪氨酸激酶对神经元发育至关重要，但它们在成人中枢神经系统中的功能尚不清楚。我们报道ErbB4在突触后密度（PSD）中富集，并与PSD-95相关。PSD-95的异源表达增强了ErbB4和MAP激酶的NRG激活。相反，抑制PSD-95在神经元中的表达会减弱nrg介导的MAP激酶激活。PSD-95与两个ErbB4分子形成三元配合物，表明PSD-95促进ErbB4二聚化。最后，NRG抑制海马CA1区长时程增强的诱导，但不影响基础突触传递。因此，NRG信号可能是突触性的，并受PSD-95调控。NRG信号在成人中枢神经系统中的作用可能是调节突触可塑性。
Neuregulins (NRGs) and their receptors, the ErbB protein tyrosine kinases, are essential for neuronal development, but their functions in the adult CNS are unknown. We report that ErbB4 is enriched in the postsynaptic density (PSD) and associates with PSD-95. Heterologous expression of PSD-95 enhanced NRG activation of ErbB4 and MAP kinase. Conversely, inhibiting expression of PSD-95 in neurons attenuated NRG-mediated activation of MAP kinase. PSD-95 formed a ternary complex with two molecules of ErbB4, suggesting that PSD-95 facilitates ErbB4 dimerization. Finally, NRG suppressed induction of long-term potentiation in the hippocampal CA1 region without affecting basal synaptic transmission. Thus, NRG signaling may be synaptic and regulated by PSD-95. A role of NRG signaling in the adult CNS may be modulation of synaptic plasticity.