农业蛋白片段诱导爪蟾胚胎肌瘤肌乙酰胆碱受体异位聚集的差异。

Journal of neurobiology Pub Date : 2000-09-15
E W Godfrey, J Roe, R D Heathcote
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引用次数: 0

摘要

Agrin是一种细胞外突触蛋白,组织神经肌肉连接处的突触后装置,包括乙酰胆碱受体(achr)。在培养中,agrin的cooh末端部分具有充分的achr聚集活性,包括G1、G2和G3三个球状结构域。含有这些结构域的部分agrin蛋白与肌肉细胞的不同细胞表面蛋白结合,包括α -歧糖聚糖(G1-G2)和硫酸肝素蛋白聚糖(G2),而G3结构域足以聚集achr。我们试图确定agin的G1和G2结构域是否在体内增强agin的活性,就像它们在培养中一样。含有G3、G2和G3或所有三个G结构域的神经元agrin亚型(4,8)的cooh末端片段在爪蟾胚胎中肌间瘤肌神经肌肉突触形成过程中过表达。编码这些大鼠agrin片段的RNA被注入单细胞胚胎。这三个片段都增加了肌组中心附近无神经支配区域achr的异位聚集。令人惊讶的是,在最小片段过表达后异位聚集更为明显,该片段缺乏肝素和α -糖醛酸异常结合域。在过表达这些片段的胚胎中,突触AChR聚集减少,表明神经末梢分泌的内源性agrin与肌肉细胞分泌的外源性agrin片段之间存在竞争。这些结果表明,较大的agrin片段与α -歧义聚糖和/或硫酸肝素蛋白聚糖结合可能会隔离片段并抑制其在胚胎肌肉中的活性。这些分子间的相互作用可能在体内调节agrin活性和神经肌肉连接的分化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Agrin fragments differentially induce ectopic aggregation of acetylcholine receptors in myotomal muscles of Xenopus embryos.

Agrin is an extracellular synaptic protein that organizes the postsynaptic apparatus, including acetylcholine receptors (AChRs), of the neuromuscular junction. The COOH-terminal portion of agrin has full AChR-aggregating activity in culture, and includes three globular domains, G1, G2, and G3. Portions of the agrin protein containing these domains bind to different cell surface proteins of muscle cells, including alpha-dystroglycan (G1-G2) and heparan sulfate proteoglycans (G2), whereas the G3 domain is sufficient to aggregate AChRs. We sought to determine whether the G1 and G2 domains of agrin potentiate agrin activity in vivo, as they do in culture. Fragments from the COOH-terminal of a neuronal agrin isoform (4,8) containing G3, both G2 and G3, or all three G domains were overexpressed in Xenopus embryos during neuromuscular synapse formation in myotomal muscles. RNA encoding these fragments of rat agrin was injected into one-cell embryos. All three fragments increased the ectopic aggregation of AChRs in noninnervated regions near the center of myotomes. Surprisingly, ectopic aggregation was more pronounced after overexpression of the smallest fragment, which lacks the heparin- and alpha-dystroglycan-binding domains. Synaptic AChR aggregation was decreased in embryos overexpressing the fragments, suggesting a competition between endogenous agrin secreted by nerve terminals and exogenous agrin fragments secreted by muscle cells. These results suggest that binding of the larger agrin fragments to alpha-dystroglycan and/or heparan sulfate proteoglycans may sequester the fragments and inhibit their activity in embryonic muscle. These intermolecular interactions may regulate agrin activity and differentiation of the neuromuscular junction in vivo.

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