Recent insights into the biological roles of mucin-type O-glycosylation

Abstract

In this special issue of the Glycoconjugate Journal focusing on glycosciences and development, we summarize recent advances in our understanding of the role of mucintype O-glycans in development and disease. The presence of this widespread protein modification has been known for decades, yet identification of its biological functions has been hampered by the redundancy and complexity of the enzyme family controlling the initiation of O-glycosylation, as well as the diversity of extensions of the core sugar. Recent studies in organisms as diverse as mammals and Drosophila have yielded insights into the function of this highly abundant and evolutionarily-conserved protein modification. Gaining an understanding of mucin-type O-glycans in these diverse systems will elucidate crucial conserved processes underlying many aspects of development and homeostasis.

The Lectin Domain of the Polypeptide GalNAc Transferase Family of Glycosyltransferases (ppGalNAc Ts) Acts as a Switch Directing Glycopeptide Substrate Glycosylation in an N- or C-terminal Direction, Further Controlling Mucin Type O-Glycosylation

“…except for ppGalNAc T3 on GPIV) does not greatly alter the pattern of glycosylation compared with the nonglycopeptide substrate. Furthermore, no consistent differences were observed between isoform classes or between transferases within a class that had different N-or 6 Note that two different incorporation time points are plotted in Fig. 7, A-C, for ppGalNAc T1, T2, and T3 and that the distributions obtained at the two different time points are identical when plotted at the same relative scale (data not shown).…”

“…Glycoproteins containing O-glycosylated mucin domains commonly function in the protection of the cell surface and the modulation of cell-cell interactions and hence play important roles, for example in inflammation, the immune response, metastasis, and tumorigenesis (2)(3)(4)(5)(6). Because the role of the mucin domain in these glycoproteins has been thought to produce a stable extended hydrophilic motif, the actual glycosylation pattern has usually been thought to be of relatively low importance.…”

“…7, A-D, shows representative plots for ppGalNAc T1, T2, T3, and T13 with glycopeptides GPIV and GPV (left-and right-hand panels, respectively, roughly scaled to approximate their relative levels of incorporation). 6 Fig . 7E shows incorporation for the control peptides, GPIV-C and GPV-C, glycosylated by ppGalNAc T13.…”

Mechanism of a cytosolic O -glycosyltransferase essential for the synthesis of a bacterial adhesion protein

“…In many cases, proteins are modified at multiple Ser/Thr residues. For example, substrates of the cytosolic OGT are often modified at Ser/Thr/Pro repeats (2,3), and secreted mucin proteins are modified at numerous Ser and Thr residues by UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (ppGalNAcTs) (6).…”

Human Urinary Glycoproteomics; Attachment Site Specific Analysis of N- and O-Linked Glycosylations by CID and ECD

“…N-and mucin-type O-glycosylations are widely accepted as the most common and structurally diverse post-translational modifications found on secreted proteins and on the extracellular parts of membrane bound proteins (12). Given that protein glycosylation is involved in various cellular processes (13)(14)(15)(16), the site-specific characterization of N-and O-linked glycosylations and identification of the modified proteins is becoming increasingly important. Urine is potentially a rich source for N-and Olinked glycoproteins derived from renal-and distal organs and represents an interesting subproteome for structural charac-terization of human glycoproteins.…”