Molecular mechanisms of Fyn-tyrosine kinase for regulating mammalian behaviors and ethanol sensitivity.
Molecular mechanisms of Fyn-tyrosine kinase for regulating mammalian behaviors and ethanol sensitivity.
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Fyn-酪氨酸激酶调节哺乳动物行为和乙醇敏感性的分子机制。
DOI：
10.1016/s0006-2952(98)00309-8
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发表时间：
1999
影响因子：
5.8
通讯作者：
T. Yagi
中科院分区：
文献类型：
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作者：
T. Yagi
Fyn是一种src相关的非受体酪氨酸激酶，缺乏Fyn的小鼠表现出多种行为障碍，如空间学习、哺乳、情绪行为和乙醇敏感性。这些小鼠也表现出形态缺陷和突触功能损伤。Fyn在哺乳类动物的中枢神经系统中从胚胎期8.5天至成人期高度表达。缺乏Fyn小鼠的药理学和电生理分析显示γ -氨基丁酸和谷氨酸能缺陷。我们在这里提出假设，这些缺陷分别由发育紊乱和Fyn缺陷引起的突触功能损伤引起。对于谷氨酸能缺陷，特别是在乙醇给药后，n -甲基-d -天冬氨酸（NMDA）依赖的功能通过Fyn恢复，与NMDA受体2B亚型的酪氨酸磷酸化平行。因此，Fyn对NMDA受体功能的调节可能在构建和调节复杂的神经回路和行为中发挥重要作用。此外，通过Fyn的结合活性分离出cadherin相关神经受体（CNR）家族。CNR-Fyn复合体也将为深入了解调控哺乳动物行为的分子机制开辟一个新的视角。
Mice lacking Fyn, a Src-related non-receptor tyrosine kinase, show impairment of various behaviors, such as spatial learning, suckling, emotional behaviors, and ethanol sensitivity. These mice also display both morphological defects and impairment of synaptic function. Fyn is highly expressed in the mammalian CNS from embryonic day 8.5 to adulthood. Pharmacological and electrophysiological analyses of mice lacking Fyn reveal gamma-aminobutyric acid and glutamatergic defects. We propose here the hypothesis that these defects are caused separately by developmental disorganization and impairment of synapse function by a deficit in Fyn. Regarding the glutamatergic defect, in particular, after ethanol administration the N-methyl-D-aspartate (NMDA)-dependent function is recovered by Fyn, paralleled with tyrosine phosphorylation of NMDA receptor 2B subtype. Thus, modulation of the NMDA receptor function by Fyn may have a significant role in building and regulating sophisticated neural circuits and behavior. In addition, the cadherin-related neural receptor (CNR) family is isolated by binding activity for Fyn. The CNR-Fyn complex will also open a new angle for gaining insight into the molecular mechanisms for regulating mammalian behavior.