Alternatively spliced isoforms of nerve- and muscle-derived agrin: Their roles at the neuromuscular junction
Alternatively spliced isoforms of nerve- and muscle-derived agrin: Their roles at the neuromuscular junction
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DOI：
10.1016/s0896-6273(00)80751-5
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发表时间：
1999-05-01
期刊：
影响因子：
16.2
通讯作者：
Sanes, JR
中科院分区：
文献类型：
--
作者：
Burgess, RW;Nguyen, QT;Sanes, JR
Agin诱导骨骼神经肌肉接头(NMJ)的突触分化；突触前和突触后的分化在缺乏它的情况下都受到严重损害。多种选择性剪接形式的集聚蛋白结合特性和生物活性不同，是由神经和肌肉细胞合成的。我们使用外科嵌合体、异构体特异性突变小鼠和神经肌肉共培养来确定突触发生所需的集聚蛋白的来源和性质。我们发现，含有Z外显子的聚集素(Z(+))是突触后分化的关键神经源性诱导剂，而含有肝素结合位点(Y+)的神经亚型和所有肌肉衍生的亚型对于突触发生的主要步骤是必不可少的。我们的结果还表明，集聚蛋白对突触前分化的需求是由其促进突触后产生或定位适当的逆行信号的能力间接调节的。
Agrin induces synaptic differentiation at the skeletal neuromuscular junction (NMJ); both pre- and postsynaptic differentiation are drastically impaired in its absence. Multiple alternatively spliced forms of agrin that differ in binding characteristics and bioactivity are synthesized by nerve and muscle cells. We used surgical chimeras, isoform-specific mutant mice, and nerve-muscle cocultures to determine the origins and nature of the agrin required for synaptogenesis. We show that agrin containing Z exons (Z(+)) is a critical nerve-derived inducer of postsynaptic differentiation, whereas neural isoforms containing a heparin binding site (Y+) and all muscle-derived isoforms are dispensable for major steps in synaptogenesis. Our results also suggest that the requirement of agrin for presynaptic differentiation is mediated indirectly by its ability to promote postsynaptic production or localization of appropriate retrograde signals.