Protein O-mannosylation in animal development and physiology: from human disorders to Drosophila phenotypes.
Protein O-mannosylation in animal development and physiology: from human disorders to Drosophila phenotypes.
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DOI：
10.1016/j.semcdb.2010.03.010
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发表时间：
2010-08
影响因子：
7.3
通讯作者：
Panin, Vladislav M.
中科院分区：
文献类型：
--
作者：
Nakamura, Naosuke;Lyalin, Dmitry;Panin, Vladislav M.
关键词：
蛋白o -甘露糖基化对哺乳动物的发育和生理有深远的影响。影响o -甘露糖基聚糖生物合成的基因突变导致先天性肌营养不良。o -甘露糖基化缺陷引发的主要病理机制是由于α-糖基化异常导致细胞与细胞外基质的相互作用受损。α-三磷酸腺苷的低糖基化损害其配体结合活性，导致肌肉变性和神经元迁移失败。最近的实验表明，存在一种补偿机制可以改善o -甘露糖基化的缺陷。然而，这些机制仍然知之甚少。甘露糖基化和糖醛酸失调途径基因在广泛的后生动物中表现出显著的进化保守性。在斑马鱼和果蝇中，这些基因的突变和下调会导致肌肉缺陷和变性，也会导致神经系统表型，这表明o -甘露糖基化在哺乳动物和低等动物中具有相似的功能。因此，未来对遗传易感模式生物（如斑马鱼和果蝇）的研究应有助于揭示哺乳动物o -甘露糖基化的分子和遗传机制及其在调节糖醛酸失调功能中的作用。
Protein O-mannosylation has a profound effect on the development and physiology of mammalian organisms. Mutations in genes affecting O-mannosyl glycan biosynthesis result in congenital muscular dystrophies. The main pathological mechanism triggered by O-mannosylation defects is a compromised interaction of cells with the extracellular matrix due to abnormal glycosylation of α-dystroglycan. Hypoglycosylation of α-dystroglycan impairs its ligand-binding activity and results in muscle degeneration and failure of neuronal migration. Recent experiments revealed the existence of compensatory mechanisms that could ameliorate defects of O-mannosylation. However, these mechanisms remain poorly understood. O-mannosylation and dystroglycan pathway genes show remarkable evolutionary conservation in a wide range of metazoans. Mutations and downregulation of these genes in zebrafish and Drosophila result in muscle defects and degeneration, also causing neurological phenotypes, which suggests that O-mannosylation has similar functions in mammals and lower animals. Thus, future studies in genetically tractable model organisms, such as zebrafish and Drosophila, should help to reveal molecular and genetic mechanisms of mammalian O-mannosylation and its role in the regulation of dystroglycan function.
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影响因子：
1.2
作者：
Dekkers, LC;van der Plas, MC;Noordermeer, JN
通讯作者：
Noordermeer, JN
影响因子：
3.5
作者：
Brockington, M;Yuva, Y;Muntoni, F
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Muntoni, F
影响因子：
9.8
作者：
Brockington, M;Blake, DJ;Muntoni, F
通讯作者：
Muntoni, F
影响因子：
9.8
作者：
Beltran-Valero de Bernabé, D;Currier, S;Brunner, HG
通讯作者：
Brunner, HG
影响因子：
4.1
作者：
Combs, AC;Ervasti, JM
通讯作者：
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