Epithelial mucins and bacterial adhesion - Carbohydrate Chemistry: Chemical and Biological Approaches - page 598

secreted mucins such as the presence of a tandem repeat rich in serine
(Ser) and threonine (Thr) residues. The membrane bound mucin family
comprises 10 members: MUC1, MUC3A/B, MUC4, MUC12, MUC13,
MUC15, MUC16, MUC17, MUC20 and MUC21. They do not have the
property to form a gel. They mainly play a role as cell surface receptors
and sensors, which translate information about external conditions into
cellular responses including proliferation, differentiation and secretion
of specialized cellular products. 5
The variable number tandem repeat (VNTR) is a common feature to
both mucin types. The number and length of each motif is highly variable
between mucins but is unique for each mucin gene (Table 1). VNTR are
rich in Ser, Thr and proline residues that are linked to a variety of O-
linked oligosaccharide side chains.

2.2 O-Glycosylation of mucins
O-Glycosylation of mucins occurs by the addition of an N-Acetyl-galac-
tosamine (GalpNAc) residue to Ser and Thr residues in the subregions of
the rough endoplasmic reticulum or in the cis-cisternae of the Golgi
apparatus. In contrast to N-Glycosylation, O-Glycosylation does not begin
with the transfer of an oligosaccharide from a dolichol precursor, but
with the addition of a single GalpNAc. After initial addition of GalpNAc
residues, O-Glycosylation proceeds with sequential addition of mono-
saccharides such as galactose (Galp), N-Acetyl-glucosamine (GlcpNAc),
fucose (Fucp), GalpNAc and sialic acid residues. Sulfate residues are also
found in the periphery of O-glycans.
In the structure of mucin O-glycans, three regions may be dis-
tinguished: core, backbone and peripheral regions, which correspond to
the different steps of O-glycans biosynthesis process. 6 Mucin O-glycans
are built from eight core structures. The core region is created by
substitution of the first GalpNAc at C3, C6 or at both positions with a-or
b-Galp at C3, b-GlcpNAc at C3 and/or C6 and a-GalpNAc at C3 or C6
(Fig. 1). This complex pattern of core types can be further complicated by
the structural diversity introduced by sialylation. N-Acetyl-neuraminic
acid (Neup5Ac), N-glycolyl-neuraminic acid (Neup5Gc) and a variety of
O-acetylated sialic acid residues can be a2,6-linked to the first GalpNAc in
the disaccharide cores 1 and 3.
The backbone regions consist of alternating Galp and GlcpNAc resi-
dues in b1,3 (for the type 1 chains) and b1,4 (for the type 2 chains)
linkages (Fig. 2). The backbone of the chains can be linear or branched,
generating i or I antigens, respectively (Fig. 2).
Fucp, Galp, GalpNAc and Neup5Ac residues are the four
monosaccharides found at the periphery or at internal positions of the
polylactosamine backbones, most often in a-anomeric configuration.
Sulfate residues are also found, substituting Galp, GalpNAc or GlcpNAc
residues. The peripheral region characterizes the mucin by conferring
specific charge to the molecule (overall negative charge) and antigenic
properties. For example, the terminal monosaccharides may form
histo-blood group antigens such as ABH and Lewis histo-blood group
structures: Lewis a (Le a , b-Galp-(1 4)-]b-GlcpNAc), Lewis b - 3)-[a-Fucp-(1 -