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神经元突触内的非受体型酪氨酸激酶底物

毛利民¹, RyanGeosling², BrianPenman², 王强^1,2,*

¹密苏里州立大学医学院基础医学系，堪萨斯城，密苏里州 64108，美国；²密苏里州立大学医学院麻醉学系，堪萨斯城，密苏里州 64108，美国

摘要

非受体型酪氨酸激酶(non-receptor tyrosine kinase, nRTK)是一个较大的激酶家族，其功能是催化蛋白的酪氨酸磷酸化。nRTK家族中的几种常见亚型，比如Src和Fyn，可以在神经系统内表达。近年来的研究表明，神经元的突触部位含有多个nRTK的底物蛋白，这些底物蛋白主要包括谷氨酸受体(离子型和代谢型谷氨酸受体)、突触后构架蛋白、突触前调节蛋白和突触富含的多种蛋白激酶。在基础或刺激的状态下，nRTK可催化这些底物蛋白内特定酪氨酸的磷酸化，从而调节这些底物蛋白的多种生理、生化和生物物理功能。因为突触内的nRTK对突触变化信号非常敏感，所以突触nRTK被认为参与了突触传导活动的强度和效率等方面的调节。

关键词： N-甲基-D-天冬氨酸受体; AMPA ; 代谢型谷氨酸受体 ; 突触后密度蛋白95 ; Src ; Fyn ; ERK ; Cdk5 ; 突触素 ; 突触蛋白 I

分类号：Q42

Local substrates of non-receptor tyrosine kinases at synaptic sites in neurons

Li-Min Mao¹, Ryan Geosling², Brian Penman², John Q. Wang^1,2,*

¹Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA；²Department of Anesthesiology, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA

Abstract

Several non-receptor tyrosine kinase (nRTK) members are expressed in neurons of mammalian brains. Among these neuron- enriched nRTKs, two Src family kinase members (Src and Fyn) are particularly abundant at synaptic sites and have been most extensively studied for their roles in the regulation of synaptic activity and plasticity. Increasing evidence shows that the synaptic subpool of nRTKs interacts with a number of local substrates, including glutamate receptors (both ionotropic and metabotropic glutamate receptors), postsynaptic scaffold proteins, presynaptic proteins, and synapse-enriched enzymes. By phosphorylating specific tyrosine residues in the intracellular domains of these synaptic proteins either constitutively or in an activity-dependent manner, nRTKs regulate these substrates in trafficking, surface expression, and function. Given the high sensitivity of nRTKs to changing synaptic input, nRTKs are considered to act as a critical regulator in the determination of the strength and efficacy of synaptic transmission.

Key words: N-methyl-D-aspartic acid; α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ; metabotropic glutamate receptor ; postsynaptic density protein 95 ; Src ; Fyn ; ERK ; Cdk5 ; synaptophysin ; synapsin I

收稿日期：2017-03-17　　录用日期：2017-09-12

通讯作者：王强　　E-mail: wangjq@umkc.edu

DOI: 10.13294/j.aps.2017.0067

引用本文：

毛利民, RyanGeosling, BrianPenman, 王强. 神经元突触内的非受体型酪氨酸激酶底物[J]. 生理学报 2017; 69 (5): 657-665.

Li-Min Mao, Ryan Geosling, Brian Penman, John Q. Wang. Local substrates of non-receptor tyrosine kinases at synaptic sites in neurons. Acta Physiol Sin 2017; 69 (5): 657-665