Major advances in understanding regulated mucin secretion from airway goblet cells have been made in the past decade in the areas of pharmacology and basic cell biology. For instance, it is now appreciated that nucleotide agonists acting locally through P2Y purinoceptors on apical membranes of surface goblet cells provide the major regulatory system for mucin secretion. Similarly, Clara cells, the primary secretory cell in the mouse airways (and human small airways), are now recognized as major mucin-secreting cells. In Clara cells, the relative lack of staining for mucosubstances reflects essentially equal baseline rates of mucin synthesis and secretion, with little to no accumulation of mucin granules in storage pools. During mucous metaplasia induced under inflammatory conditions, mucin synthesis is massively upregulated in Clara cells, and stored mucin granules come to dominate the secretory cell phenotype. More importantly, we have seen a transition in the past few years from a pharmacological focus on regulated mucin secretion to a more molecular mechanistic focus that has great promise going forward. In part, these advances are occurring through the use of well-differentiated primary human bronchial epithelial cell cultures, but recent work in mouse models perhaps has had the most important impact. Emerging data from Munc13-2- and synaptotagmin 2-deficient mouse models represent the first direct, molecular-level manipulations of proteins involved in regulated secretory cell mucin secretion. These new data indicate that Munc13-2 is responsible for regulating a baseline mucin secretory pathway in the airways and is not essential for purinergic agonist-induced mucin secretion. In contrast, synaptotagmin 2, a fast Ca2+ sensor for the SNARE complex, is essential for regulated secretion. Interestingly, these early results suggest that there are two pathways for excocytic mucin release from goblet cells.

中文翻译：

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调节气道杯状细胞黏蛋白的分泌。

在过去的十年中，在药理学和基础细胞生物学领域，在理解气道杯状细胞分泌的粘蛋白分泌方面取得了重大进展。例如，现在可以理解，通过P2Y嘌呤受体在表面杯状细胞的顶膜上局部起作用的核苷酸激动剂为粘蛋白的分泌提供了主要的调节系统。同样，克拉拉细胞是小鼠呼吸道（和人类小呼吸道）的主要分泌细胞，现已被认为是主要的粘蛋白分泌细胞。在Clara细胞中，粘液物质的相对缺乏染色反映了粘蛋白合成和分泌的基本速率基本相等，几乎没有粘液颗粒在储存池中积聚。在炎症条件下诱发的黏膜上皮化生过程中，黏蛋白的合成在Clara细胞中大量上调，储存的粘蛋白颗粒占主导地位的分泌细胞表型。更重要的是，在过去的几年中，我们已经看到了从对调节粘蛋白分泌的药理学关注向更加有希望的分子机制关注的转变。这些进展部分地是通过使用高度分化的原代人支气管上皮细胞培养物实现的，但是最近在小鼠模型中的工作可能产生了最重要的影响。来自Munc13-2-和synaptotagmin 2缺陷小鼠模型的新数据代表了参与调节的分泌性细胞粘蛋白分泌的蛋白质的首次直接，分子水平的操作。这些新数据表明，Munc13-2负责调节气道中的基线粘蛋白分泌途径，而对于嘌呤能激动剂诱导的粘蛋白分泌并不是必需的。相反，突触结合蛋白2（一种用于SNARE复合体的快速Ca2 +传感器）对于调节分泌至关重要。有趣的是，这些早期结果表明，从杯状细胞中释放出粘性黏蛋白有两种途径。