DYSTROGLYCAN上的LARGE甘氨酸作为可调节的矩阵支架,以防止衰变
Matthew M Goddeeris1, Biming Wu, David Venzke
11] Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA [2] Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA.
Nature
|October 18, 2013
概括
对于骨肌肉功能来说,dystroglycan上的LARGE-glycan链的长度至关重要. 延长这些链条可以增强细胞外基质的结合,防止肌肉衰竭.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 发育生物学 发展生物学
背景情况:
- 细胞表面的甘氨酸层对细胞功能至关重要,并且具有高度的动态.
- 类似乙烯基葡萄糖氨基基转移酶 (LARGE) 类酶将重复的多糖体单元 (LARGE-glycan) 添加到dystroglycan中,这对其细胞外矩阵受体功能至关重要.
- 大型甘氨酸的缺陷会导致肌肉发育不良,但甘氨酸链长度的确切作用尚不清楚.
研究的目的:
- 研究LARGE-glycan重复的细胞功能及其与肌肉衰竭的相关性.
- 确定LARGE-glycan链延伸如何影响dystroglycan的细胞外矩阵结合能力.
- 阐明LARGE-glycan在骨肌肉发育和再生中的作用.
主要方法:
- 在分化小鼠肌肉中研究了Large和dystroglycan的协调上调.
- 利用合成的LARGE-glycan重复来评估与细胞外矩阵连接体的结合能力.
- 阻塞 在小鼠肌肉再生过程中大幅上调调节,以观察对dystroglycan和肌肉功能的影响.
主要成果:
- 大型和二氧化甘的协调上调促进了LARGE-glycan链的快速扩展.
- 增加LARGE-glycan链长度与加强与细胞外矩阵连接体的结合直接相关.
- 阻断 肌肉再生期间大量上调导致LARGE-glycan减少,导致底层膜缺陷,不成熟的神经肌肉结节和肌肉功能障碍.
- 患有严重肌肉衰竭的患者表现出较少的LARGE-glycan重复.
结论:
- 在dystroglycan上的LARGE-glycan可以作为细胞外基因蛋白的调节性支架.
- 大型甘氨酸链的延伸对于正常的骨肌肉功能和完整性至关重要.
- 功能障碍的LARGE-glycan延伸有助于肌肉发育不良的病原体.
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