Mucin O-Glycan Branching Enzymes: Structure, Function, and Gene Regulation

Abstract

AbstractMucin O-glycans are conjugated carbohydrate chains that contain at the reducing terminus N-acetylgalactosamine linked covalently to serine/threonine in the peptide backbone. They are found in mucins and many nonmucin glycoproteins. The presence of a tandem repeat peptide heavily glycosylated with mucin O-glycans distinguishes mucins from other glycoproteins that contain mucin O-glycans. Muc14, -15, and -18, which do not contain a tandem repeat peptide, are the exceptions. To date, about six secreted and 14 membrane-tethered mucins have been reported based on cloned complementary DNA (cDNA) sequences [1, 2]. The functions of mucin O-glycans vary according to where they reside. For secreted mucins, O-glycans can retain water, maintain the viscoelastic properties of mucus secretion, and bind and clear inhaled and ingested pathogens, such as mycoplasma [3, 4], viruses [5], and bacteria [6]. This function depends primarily on heterogeneous carbohydrates, while the other two functions are determined by high carbohydrate content. High carbohydrate content and very heterogeneous carbohydrate structures found in secreted mucins enable them to perform the first line of innate immune defense at the epithelial surface of many mucus-secretory tissues, such as airways and the gastrointestinal tract. Under pathological conditions, overproduction of secreted mucins coupled with poor clearance of mucus causes obstructive lung diseases [7].KeywordsMucin O-glycanBranching enzymesC2GnT ­b6N-acetylglucosaminyltransferase