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首页> 外文期刊>The European Journal of Neuroscience >Correct expression and localization of collagen XIII are crucial for the normal formation and function of the neuromuscular system
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Correct expression and localization of collagen XIII are crucial for the normal formation and function of the neuromuscular system

机译：胶原乳糖XIII的正确表达和定位对于神经肌肉系统的正常形成和功能至关重要

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Transmembrane collagen XIII has been linked to maturation of the musculoskeletal system. Its absence in mice (Col13a1(-/-)) results in impaired neuromuscular junction (NMJ) differentiation and function, while transgenic overexpression (Col13a1(oe)) leads to abnormally high bone mass. Similarly, loss-of-function mutations in COL13A1 in humans produce muscle weakness, decreased motor synapse function and mild dysmorphic skeletal features. Here, analysis of the exogenous overexpression of collagen XIII in various muscles revealed highly increased transcript and protein levels, especially in the diaphragm. Unexpectedly, the main location of exogenous collagen XIII in the muscle was extrasynaptic, in fibroblast-like cells, while some motor synapses were devoid of collagen XIII, possibly due to a dominant negative effect. Concomitantly, phenotypical changes in the NMJs of the Col13a1(oe) mice partly resembled those previously observed in Col13a1(-/-) mice. Namely, the overall increase in collagen XIII expression in the muscle produced both pre- and postsynaptic abnormalities at the NMJ, especially in the diaphragm. We discovered delayed and compromised acetylcholine receptor (AChR) clustering, axonal neurofilament aggregation, patchy acetylcholine vesicle (AChV) accumulation, disrupted adhesion of the nerve and muscle, Schwann cell invagination and altered evoked synaptic function. Furthermore, the patterns of the nerve trunks and AChR clusters in the diaphragm were broader in the adult muscles, and already prenatally in the Col13a1(oe) mice, suggesting collagen XIII involvement in the development of the neuromuscular system. Overall, these results confirm the role of collagen XIII at the neuromuscular synapses and highlight the importance of its correct expression and localization for motor synapse formation and function.
机译：跨膜胶原蛋白XIII与肌肉骨骼系统的成熟有关。它在小鼠中的缺失（COL13A1（ - / - ））导致神经肌肉结（NMJ）分化和功能受损，而转基因过表达（COL13A1（OE））导致异常高的骨质量。类似地，人类COL13A1中的功能突变突变产生肌肉弱点，降低电动机突触功能和轻度疑难垂骨骼特征。在此，分析各种肌肉中胶原氧化胶的外源表达揭示了高度增加的转录物和蛋白质水平，特别是在隔膜中。出乎意料地，在成纤维细胞样细胞中，肌肉外源胶原氧化物XIII的主要位置是突触，而一些电动机突触缺乏胶原氧化物XIII，可能是由于显性负面影响。同时，Col13A1（OE）小鼠的NMJ的表型变化部分类似于在Col13A1（ - / - ）小鼠中观察到的那些。即，肌肉中胶原氧化物XIII表达的总体增加在NMJ中产生了前后异常，特别是在隔膜中。我们发现止吐和受损的乙酰胆碱受体（ACHR）聚类，轴突神经膜聚集，斑块乙酰胆碱囊泡（ACHV）积累，破坏神经和肌肉的粘附，Schwann细胞内部术，改变诱发的突触功能。此外，隔膜中的神经树干和ACHR簇的图案在成人肌肉中更宽，并且在COL13A1（OE）小鼠中已经是产前的，表明胶原蛋白XIII受累于神经肌肉系统的发育。总体而言，这些结果证实了胶原蛋白XIII在神经肌肉突触处的作用，并突出了其对电动机突触形成和功能的正确表达和定位的重要性。

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