Spatiotemporal diversity and regulation of glycosaminoglycans in cell homeostasis and human disease.
Spatiotemporal diversity and regulation of glycosaminoglycans in cell homeostasis and human disease.
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DOI：
10.1152/ajpcell.00085.2022
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发表时间：
2022-05-01
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影响因子：
--
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中科院分区：
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糖胺聚糖(GAG)是一种长而线性的多糖，广泛表达在细胞表面和所有动物细胞的细胞外基质中。这些复杂的碳水化合物在许多细胞过程中发挥着重要作用，并与许多疾病状态有关，包括癌症、炎症和遗传性疾病。GAG是生物学中最复杂的分子之一，具有巨大的信息量和广泛的结构和功能异质性。GAG的生物合成是一个非模板驱动的过程，在过去的几十年里，人们已经广泛地研究了一大群生物合成酶。有趣的是，这些酶的表达以及随后的多糖链的结构和功能在发育过程中和某些病理生理条件下可以在时间和空间上发生变化，这表明它们的组装在细胞中受到严格的调控。由于其在细胞内稳态和疾病中的许多关键作用，人们对将其作为一种治疗方法的组装和功能非常感兴趣。基因组学和GAG分析技术的最新进展推动了这一领域的发展，并为哺乳动物糖基化调控提供了新的视角。这篇综述重点介绍了GAG的时空多样性及其在人类生物学和疾病中指导其组装和功能的机制。
Glycosaminoglycans (GAGs) are long, linear polysaccharides that are ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These complex carbohydrates play important roles in many cellular processes and have been implicated in many disease states, including cancer, inflammation, and genetic disorders. GAGs are among the most complex molecules in biology with enormous information content and extensive structural and functional heterogeneity. GAG biosynthesis is a nontemplate-driven process facilitated by a large group of biosynthetic enzymes that have been extensively characterized over the past few decades. Interestingly, the expression of the enzymes and the consequent structure and function of the polysaccharide chains can vary temporally and spatially during development and under certain pathophysiological conditions, suggesting their assembly is tightly regulated in cells. Due to their many key roles in cell homeostasis and disease, there is much interest in targeting the assembly and function of GAGs as a therapeutic approach. Recent advances in genomics and GAG analytical techniques have pushed the field and generated new perspectives on the regulation of mammalian glycosylation. This review highlights the spatiotemporal diversity of GAGs and the mechanisms guiding their assembly and function in human biology and disease.
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