Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus.
Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus.
复制标题
多个EPHB受体酪氨酸激酶在海马中塑造树突状刺。
DOI：
10.1083/jcb.200306033
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发表时间：
2003-12-22
影响因子：
7.8
通讯作者：
Ethell, Iryna M
中科院分区：
文献类型：
--
作者：
Henkemeyer, Mark;Itkis, Olga S;Ngo, Michelle;Hickmott, Peter W;Ethell, Iryna M
在这里，使用遗传学的方法，我们剖析了EphB受体酪氨酸激酶在树突棘发育中的作用。对EphB1、EphB2和EphB3双重和三重突变小鼠在不同组合中缺乏这些受体的分析表明，尽管这三种受体在不同程度上参与了海马树突棘的形态发生和突触的形成。缺乏EphB表达的海马神经元在体外不能形成树突棘，而在体内形成异常的刺。突变体中脊柱形成的缺陷与兴奋性谷氨酸能突触的急剧减少以及NMDA和AMPA受体的聚集有关。我们进一步证明，EphB2中的激酶缺陷、截断突变也会导致脊柱的异常发育，并且EphB受体的激活可以加速树突棘的发育。这些结果表明，EphB受体细胞的自主前向信号参与了海马神经元树突棘的形成和突触的成熟。
Here, using a genetic approach, we dissect the roles of EphB receptor tyrosine kinases in dendritic spine development. Analysis of EphB1, EphB2, and EphB3 double and triple mutant mice lacking these receptors in different combinations indicates that all three, although to varying degrees, are involved in dendritic spine morphogenesis and synapse formation in the hippocampus. Hippocampal neurons lacking EphB expression fail to form dendritic spines in vitro and they develop abnormal spines in vivo. Defective spine formation in the mutants is associated with a drastic reduction in excitatory glutamatergic synapses and the clustering of NMDA and AMPA receptors. We show further that a kinase-defective, truncating mutation in EphB2 also results in abnormal spine development and that ephrin-B2–mediated activation of the EphB receptors accelerates dendritic spine development. These results indicate EphB receptor cell autonomous forward signaling is responsible for dendritic spine formation and synaptic maturation in hippocampal neurons.