Inhibitory machinery for the functional dystroglycan glycosylation
Inhibitory machinery for the functional dystroglycan glycosylation
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功能性肌营养不良聚糖糖基化的抑制机制
DOI：
10.1093/jb/mvad003
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Okajima Tetsuya
中科院分区：
文献类型：
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作者：
Kondo Yuji;Okajima Tetsuya
肌营养不良聚糖（DG）是一种跨膜蛋白，在将细胞外基质来源的信号转导至细胞骨架中起关键作用，并为骨骼肌细胞膜提供物理强度。DG的胞外结构域α-DG具有独特的糖基化模式。该结构域与细胞外基质组分（包括层粘连蛋白）相互作用需要全功能糖基化。在DG上的这种功能性聚糖中发现的独特糖组成之一是两种核糖醇磷酸盐，其通过使用CDP-核糖醇作为供体底物的fuketin（FKTN）和fukutin-related protein（FKRP）的顺序作用转移。然后这些进一步引发基质聚糖生物合成。最近的一项体外研究报告，如果使用CDP-甘油（CDP-Gro）作为供体底物，则FKTN和FKRP可将甘油磷酸盐类似地添加到α-DG中。然而，这些发现的生理相关性仍然难以捉摸。Imae等人解决了关于CDP-Gro是否存在于哺乳动物中以及CDP-Gro如何在哺乳动物中合成和发挥作用的知识差距。
Dystroglycan (DG), a muscular transmembrane protein, plays a critical role in transducing extracellular matrix-derived signals to the cytoskeleton and provides physical strength to skeletal muscle cell membranes. The extracellular domain of DG, α-DG, displays unique glycosylation patterns. Fully functional glycosylation is required for this domain to interact with components of extracellular matrices, including laminin. One of the unique sugar compositions found in such functional glycans on DG is two ribitol phosphates that are transferred by the sequential actions of fukutin (FKTN) and fukutin-related protein (FKRP), which use CDP-ribitol as a donor substrate. These are then further primed for matriglycan biosynthesis. A recentin vitrostudy reported that glycerol phosphate could be similarly added to α-DG by FKTN and FKRP if they used CDP-glycerol (CDP-Gro) as a donor substrate. However, the physiological relevance of these findings remains elusive. Imae et al. addressed the knowledge gap regarding whether CDP-Gro is present in mammals and how CDP-Gro is synthesized and functions in mammals.