Integrins mediate functional pre- and postsynaptic maturation at a hippocampal synapse
Integrins mediate functional pre- and postsynaptic maturation at a hippocampal synapse
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DOI：
10.1038/35077101
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发表时间：
2001-05-17
期刊：
影响因子：
64.8
通讯作者：
Westbrook, G
中科院分区：
文献类型：
--
作者：
Chavis, P;Westbrook, G
突触前终末与其突触后靶点之间的协调信号传导对于中枢突触的发育和功能至关重要。除了可扩散的分子（1），这种双向信息流可能涉及通过细胞粘附分子的直接相互作用（2，3）。在这里，我们表明，一类细胞粘附分子，整合素，需要在体外海马突触的功能成熟。在未成熟的突触，谷氨酸释放（P-r）的概率高，与表达的突触后NMDA（N-甲基-D-天冬氨酸）受体含有NR 2B亚单位。P-r的活性依赖性降低和突触NMDA受体亚基组成的开关通过含有整合素结合位点Arg-Gly-Asp（RGD）的肽的慢性阻断或通过针对β 3整合素亚基的功能性抗体来防止。通过对突触结合蛋白I的管腔内结构域的抗体的摄取来监测活性突触，也具有β 3亚基免疫反应性。我们的研究结果提供了证据，整合素介导的信号是必不可少的精心策划的成熟的中央兴奋性突触。
Coordinated signalling between presynaptic terminals and their postsynaptic targets is essential for the development and function of central synapses. In addition to diffusible molecules(1), this bidirectional flow of information could involve direct interactions through cell-adhesion molecules(2,3). Here, we show that one class of cell-adhesion molecule, the integrins, are required for the functional maturation of hippocampal synapses in vitro. At immature synapses, a high probability of glutamate release (P-r) was correlated with the expression of postsynaptic NMDA (N-methyl-D-aspartate) receptors containing the NR2B subunit. The activity-dependent reduction in P-r and a switch in the subunit composition of synaptic NMDA receptors was prevented by chronic blockade with peptides containing the integrin-binding site Arg-Gly-Asp (RGD), or by a functional antibody against the beta3 integrin subunit. Active synapses, monitored by the uptake of antibodies against the intraluminal domain of synaptotagmin I, also had beta3 subunit immunoreactivity. Our results provide evidence that integrin-mediated signalling is essential for the orchestrated maturation of central excitatory synapses.