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首页> 外文期刊>Biochemical Pharmacology >Molecular mechanisms of Fyn-tyrosine kinase for regulating mammalian behaviors and ethanol sensitivity.
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Molecular mechanisms of Fyn-tyrosine kinase for regulating mammalian behaviors and ethanol sensitivity.

机译: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。

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摘要

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.
机译:缺乏Fyn(一种与Src相关的非受体酪氨酸激酶)的小鼠表现出多种行为受损,例如空间学习,哺乳,情绪行为和乙醇敏感性。这些小鼠还显示出形态缺陷和突触功能受损。从胚胎第8.5天到成年,Fyn在哺乳动物CNS中高表达。缺乏Fyn的小鼠的药理和电生理分析表明,γ-氨基丁酸和谷氨酸能缺陷。我们在这里提出这样的假设,即这些缺陷分别由发育紊乱和Fyn缺陷引起的突触功能损害引起。关于谷氨酸能缺陷,特别是在给予乙醇后,通过Fyn恢复了N-甲基-D-天冬氨酸(NMDA)依赖性功能,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建立和调节复杂的神经回路和行为中起重要作用。另外,通过对Fyn的结合活性来分离钙粘蛋白相关的神经受体(CNR)家族。 CNR-Fyn复合物也将为了解调节哺乳动物行为的分子机制开辟一个新的角度。

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