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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Evidence of an agrin receptor in cortical neurons.
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Evidence of an agrin receptor in cortical neurons.

机译：皮质神经元中凝集素受体的证据。

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Agrin plays a key role in directing the differentiation of the vertebrate neuromuscular junction. Understanding agrin function at the neuromuscular junction has come via molecular genetic analyses of agrin as well as identification of its receptor and associated signal transduction pathways. Agrin is also expressed by many populations of neurons in brain, but its role remains unknown. Here we show, in cultured cortical neurons, that agrin induces expression of the immediate early gene c-fos in a concentration-dependent and saturable manner, as expected for a signal transduction pathway activated by a cell surface receptor. Agrin is active in cortical neurons at picomolar concentrations, is Ca(2+) dependent, and is inhibited by heparin and staurosporine. Despite marked differences in acetylcholine receptor (AChR)-clustering activity, all alternatively spliced forms of agrin are equally potent inducers of c-fos in cortical neurons. A similar, isoform-independent response to agrin was also observed in cultures prepared from the hippocampus and cerebellum. Only agrin with high AChR-clustering activity was effective in cultured muscle, whereas non-neuronal cells were agrin insensitive. Although consistent with a receptor tyrosine kinase model similar to the muscle-specific kinase-myotube-associated specificity component complex in muscle, our data suggest that CNS neurons express a unique agrin receptor. Evidence that neuronal signal transduction is mediated via an increase in intracellular Ca(2+) means that agrin is well situated to influence important Ca(2+)-dependent functions in brain, including neuronal growth, differentiation, and adaptive changes in gene expression associated with synaptic remodeling.
机译：Agrin在指导脊椎动物神经肌肉接头的分化中起关键作用。了解神经肌肉接头处的凝集素功能已经通过对凝集素的分子遗传分析以及其受体和相关信号转导途径的鉴定来进行。大脑中许多神经元群体也表达了Agrin，但其作用仍然未知。在这里，我们显示了在培养的皮质神经元中，如细胞表面受体激活的信号转导途径所期望的那样，凝集素以浓度依赖性和饱和性方式诱导立即早期基因c-fos的表达。 Agrin在皮摩尔浓度的皮层神经元中活跃，是Ca（2+）依赖性的，并被肝素和星形孢菌素抑制。尽管在乙酰胆碱受体（AChR）群集活性方面有显着差异，但凝集素的所有其他剪接形式都是皮质神经元中c-fos的有效诱导剂。在从海马和小脑制备的培养物中，也观察到了类似的，不依赖亚型的对凝集素的反应。只有具有高AChR簇活性的凝集素在培养的肌肉中有效，而非神经元细胞对凝集素不敏感。尽管与类似于肌肉中与肌肉特异性激酶-肌管相关的特异性成分复合物的受体酪氨酸激酶模型相一致，但我们的数据表明中枢神经系统神经元表达独特的凝集素受体。神经元信号转导是通过细胞内Ca（2+）的增加来介导的证据表明，凝集素处于良好位置，可影响大脑中重要的Ca（2+）依赖性功能，包括神经元的生长，分化和基因表达相关的适应性变化与突触重塑。

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