Intracellular Processing of Human Secreted Polymeric Airway Mucins.
Intracellular Processing of Human Secreted Polymeric Airway Mucins.
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DOI：
10.1513/annalsats.201802-143aw
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发表时间：
2018-11
影响因子：
8.3
通讯作者：
Ridley C
中科院分区：
文献类型：
--
作者：
Thornton DJ;Sharpe C;Ridley C
粘膜纤毛清除是肺先天防御的重要组成部分。在呼吸系统疾病如哮喘、慢性阻塞性肺病和囊性纤维化中，具有异常性质的粘液有助于阻塞气道。粘液在气道清除和病原体保护中的功能失效导致慢性感染和死亡风险。聚合粘蛋白（MUC 5AC和MUC 5 B）提供气道粘液凝胶的结构框架。这些巨大的多聚O-连接糖蛋白的细胞内合成和组装是一个复杂的多阶段过程，涉及分子内和分子间二硫键的形成和O-聚糖链的大量添加。完全形成的聚合物以高度组织化和浓缩的形式包装在特化分泌细胞内的分泌颗粒内，并且在适当的刺激粘蛋白释放并膨胀以形成粘液后。这篇简短的文章将汇集目前的知识，在生产粘蛋白聚合物的不同步骤和分子机制，凝聚成一个包装形式的分泌颗粒。通过解开控制细胞内粘蛋白超分子结构的分子机制，我们可能会对健康和疾病中决定粘液凝胶特性的因素有新的认识。
Mucociliary clearance is a crucial component of innate defense of the lung. In respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis, mucus with abnormal properties contributes to obstruction of the airways. The failure in function of mucus in airway clearance and pathogen protection leads to chronic infection and risk of death. Polymeric mucins (MUC5AC and MUC5B) provide the structural framework of the airway mucus gel. The intracellular synthesis and assembly of these enormous, polymeric O-linked glycoproteins is a complex, multi-stage process involving intra- and intermolecular disulfide bond formation and extensive addition of O-glycan chains. The fully formed polymers are packaged in a highly organized and condensed form within secretory granules inside specialized secretory cells, and after the appropriate stimulus mucins are released and expand to form mucus. This short article will bring together the current knowledge on the different steps in the production of mucin polymers and the molecular mechanisms that condense them into a packaged form in secretory granules. It is by unravelling the molecular mechanisms that control intracellular mucin supramolecular structure that we might gain new insight into what determines mucus gel properties in health and disease.