Agrin binds to the nerve-muscle basal lamina via laminin.
Agrin binds to the nerve-muscle basal lamina via laminin.
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DOI：
10.1083/jcb.137.3.671
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发表时间：
1997-05-05
期刊：
影响因子：
--
通讯作者：
Ruegg MA
中科院分区：
文献类型：
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作者：
Denzer AJ;Brandenberger R;Gesemann M;Chiquet M;Ruegg MA
聚集蛋白是一种硫酸乙酰肝素蛋白聚糖，是形成和维持神经肌肉接头所必需的。在发育过程中，聚集蛋白从运动神经元分泌，以触发乙酰胆碱受体（AChR）和肌纤维中的其他蛋白质的局部聚集，它们共同组成突触后装置。从运动神经元释放后，聚集蛋白结合到发育中的肌肉基底层，并在整个成年期保持与突触部分的联系。我们最近已经证明全长鸡聚集蛋白与称为Matrigel™的基底膜样制剂结合。从NH 2末端的前130个氨基酸是必要的结合，他们的原因，在培养的鸡肌管，全长聚集蛋白诱导的AChR集群是小的。在本报告中，我们表明含有这130个氨基酸的聚集蛋白的NH 2-末端片段足以结合Matrigel™，并且与该制剂的结合是由层粘连蛋白-1介导的。该片段还结合层粘连蛋白-2和-4，肌纤维基底层的主要层粘连蛋白同种型。在培养的肌管上，它与层粘连蛋白共定位，并富含AChR聚集体。此外，我们表明，全长聚集蛋白的AChR集群的大小的影响是逆转的存在下的NH 2-末端聚集蛋白片段。这些数据有力地表明，结合的聚集蛋白层粘连蛋白提供了基础，其本地化的突触基底层和其他基底膜。
Agrin is a heparan sulfate proteoglycan that is required for the formation and maintenance of neuromuscular junctions. During development, agrin is secreted from motor neurons to trigger the local aggregation of acetylcholine receptors (AChRs) and other proteins in the muscle fiber, which together compose the postsynaptic apparatus. After release from the motor neuron, agrin binds to the developing muscle basal lamina and remains associated with the synaptic portion throughout adulthood. We have recently shown that full-length chick agrin binds to a basement membrane-like preparation called Matrigel™. The first 130 amino acids from the NH2 terminus are necessary for the binding, and they are the reason why, on cultured chick myotubes, AChR clusters induced by full-length agrin are small. In the current report we show that an NH2-terminal fragment of agrin containing these 130 amino acids is sufficient to bind to Matrigel™ and that the binding to this preparation is mediated by laminin-1. The fragment also binds to laminin-2 and -4, the predominant laminin isoforms of the muscle fiber basal lamina. On cultured myotubes, it colocalizes with laminin and is enriched in AChR aggregates. In addition, we show that the effect of full-length agrin on the size of AChR clusters is reversed in the presence of the NH2-terminal agrin fragment. These data strongly suggest that binding of agrin to laminin provides the basis of its localization to synaptic basal lamina and other basement membranes.