Dept. Medical Biochemistry, University of Gothenburg, Box 440, 40530 Gothenburg, Sweden.
Dept. Medical Biochemistry, University of Gothenburg, Box 440, 40530 Gothenburg, Sweden
J Cell Sci. 2020 Mar 13;133(5):jcs240929. doi: 10.1242/jcs.240929.
Membrane mucins cover most mucosal surfaces throughout the human body. The intestine harbors complex population of microorganisms (the microbiota) and numerous exogenous molecules that can harm the epithelium. In the colon, where the microbial burden is high, a mucus barrier forms the first line of defense by keeping bacteria away from the epithelial cells. In the small intestine where the mucus layer is less organized, microbes are kept at bay by peristalsis and antimicrobial peptides. Additionally, a dense glycocalyx consisting of extended and heavily glycosylated membrane mucins covers the surface of enterocytes. Whereas many aspects of mucosal barriers are being discovered, the function of membrane mucins remains a largely overlooked topic, mainly because we lack the necessary reagents and experimental animal models to investigate these large glycoproteins. In this Cell Science at a Glance article and accompanying poster, we highlight central concepts of membrane mucin biology and the role of membrane mucins as integral components of intestinal mucosal barriers. We also present the current consensus concerning the role of membrane mucins in host-microbe interactions. Moreover, we discuss how regulatory circuits that govern membrane mucins in the healthy gut display strong overlap with pathways that are perturbed during chronic inflammation. Finally, we review how dysregulation of intestinal membrane mucins may contribute to human diseases, such as inflammation and cancer.
黏膜糖蛋白覆盖着人体大部分黏膜表面。肠道内栖息着复杂的微生物群（微生物组）和大量可能伤害上皮细胞的外源性分子。在微生物负荷量高的结肠中，黏液屏障通过将细菌与上皮细胞隔离来形成第一道防线。在黏液层组织化程度较低的小肠中，蠕动和抗菌肽可将微生物阻挡在一定范围之外。此外，由伸展和高度糖基化的膜黏液蛋白组成的密集糖萼覆盖着肠细胞的表面。尽管黏膜屏障的许多方面正在被发现，但膜黏液蛋白的功能仍然是一个很大程度上被忽视的课题，主要是因为我们缺乏必要的试剂和实验动物模型来研究这些大型糖蛋白。在本期《细胞科学一瞥》文章及其配套海报中，我们重点介绍了膜黏液蛋白生物学的核心概念，以及膜黏液蛋白作为肠道黏膜屏障不可或缺的组成部分的作用。我们还介绍了目前关于膜黏液蛋白在宿主-微生物相互作用中作用的共识。此外，我们还讨论了调控肠道健康中膜黏液蛋白的调控回路与在慢性炎症期间失调的通路之间的强烈重叠。最后，我们综述了肠道膜黏液蛋白失调如何可能导致人类疾病，如炎症和癌症。
