Department of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Department of Internal Medicine, Washington University School of Medicine, St Louis, United States.
Elife. 2021 Oct 22;10:e67292. doi: 10.7554/eLife.67292.
Intestinal goblet cells maintain the protective epithelial barrier through mucus secretion and yet sample lumenal substances for immune processing through formation of goblet cell associated antigen passages (GAPs). The cellular biology of GAPs and how these divergent processes are balanced and regulated by goblet cells remains unknown. Using high-resolution light and electron microscopy, we found that in mice, GAPs were formed by an acetylcholine (ACh)-dependent endocytic event remarkable for delivery of fluid-phase cargo retrograde into the trans-golgi network and across the cell by transcytosis - in addition to the expected transport of fluid-phase cargo by endosomes to multi-vesicular bodies and lysosomes. While ACh also induced goblet cells to secrete mucins, ACh-induced GAP formation and mucin secretion were functionally independent and mediated by different receptors and signaling pathways, enabling goblet cells to differentially regulate these processes to accommodate the dynamically changing demands of the mucosal environment for barrier maintenance and sampling of lumenal substances.
肠杯状细胞通过分泌黏液来维持保护性上皮屏障，同时通过形成杯状细胞相关抗原通道（GAPs）来对腔内容物进行免疫处理。GAP 的细胞生物学特性，以及杯状细胞如何平衡和调节这些不同的过程，目前尚不清楚。我们使用高分辨率的光和电子显微镜发现，在小鼠中，GAP 是通过乙酰胆碱（ACh）依赖性的内吞作用形成的，这种作用显著地将液相等货物逆行运输到反式高尔基体网络，并通过胞吞作用穿过细胞——除了液相等货物通过内体运输到多泡体和溶酶体的预期运输方式之外。虽然 ACh 也能诱导杯状细胞分泌粘蛋白，但 ACh 诱导的 GAP 形成和粘蛋白分泌在功能上是独立的，由不同的受体和信号通路介导，使杯状细胞能够有区别地调节这些过程，以适应黏膜环境对屏障维持和腔内容物采样的动态变化需求。
