Mucins and the Microbiome

Abstract

Generating the barriers that protect our inner surfaces from bacteria and other challenges requires large glycoproteins called mucins. These come in two types, gel-forming and transmembrane, all characterized by large, highly O-glycosylated mucin domains that are diversely decorated by Golgi glycosyltransferases to become extended rodlike structures. The general functions of mucins on internal epithelial surfaces are to wash away microorganisms and, even more importantly, to build protective barriers. The latter function is most evident in the large intestine, where the inner mucus layer separates the numerous commensal bacteria from the epithelial cells. The host's conversion of MUC2 to the outer mucus layer allows bacteria to degrade the mucin glycans and recover the energy content that is then shared with the host. The molecular nature of the mucins is complex, and how they construct the extracellular complex glycocalyx and mucus is poorly understood and a future biochemical challenge.

Mucus barrier, mucins and gut microbiota: the expected slimy partners?

“…The amino acid Pro, instead, ensures that the structure of the mucins remains unfolded in the Golgi apparatus, allowing the O-glycosylation process (all the chemical steps are detailed in figures 1 and 2 ). 1 5 More than 80% of the mucin mass is made up of O-glycans and O-glycosylation is the main modification and type of glycosylation that affects mucins. 1 6 7 O-glycosylation represents an important process allowing the creation of a glycan coat, hiding the protein core of the mucins and protecting it from endogenous protease degradation, in addition to conferring the capacity to bind and be soluble in water and to form a gel.…”

“… 1 5 More than 80% of the mucin mass is made up of O-glycans and O-glycosylation is the main modification and type of glycosylation that affects mucins. 1 6 7 O-glycosylation represents an important process allowing the creation of a glycan coat, hiding the protein core of the mucins and protecting it from endogenous protease degradation, in addition to conferring the capacity to bind and be soluble in water and to form a gel. 1 7 8 Glycosylation differs along the different regions of the digestive tract and among individuals, depending on the expression of glycosyltransferases, the state of health or disease and microbial colonisation.…”

“…This review intends to discuss one of the key components of gut barrier integrity, that is, the mucus, which cover the intestinal epithelial surface. The mucus is composed of many components: water (90%–95%), 1 2 electrolytes, lipids (1%–2%), proteins and others. 3 This mucus is a dilute, aqueous and viscoelastic secretion, thanks to specific mucus proteins that are called mucins and are the major structural and functional components present in the mucus at a concentration of 1%–5%.…”

Microbe–Mucus Interface in the Pathogenesis of Colorectal Cancer

“…As a physical barrier, it separates external substances, enzymes, and bacteria from the epithelium. It was recently suggested that intestinal mucus forms three lines of defense against bacteria [22]. Firstly, through the physical inner mucus layer barrier, secondly, via the sentinel goblet cell response, and thirdly, through the crypt goblet cellemptying response.…”

Revealing the human mucinome

“…Mucin domains are modular protein domains that adopt rigid and extended bottle-brush like structures due to a high density of O-glycosylated serine and threonine residues [1][2][3] . Mucin-type O-glycans are characterized by an initiating α-N-acetylgalactosamine (α-GalNAc) monosaccharide that can be further elaborated into several core structures through complex regulation of glycosyltransferases 4,5 .…”