Intestinal mucins 'soluble and insoluble problems'

Abstract: Highly glycosylated glycoproteins – mucins – are the major constituents of the mucus layer and glycocalyx that cover mucosal surfaces. Twelve human mucin genes have been identified, and the mucins may be divided into those that are membraneassociated and those that are secreted. Among the latter, the oligomeric mucins are responsible for mucus formation. The various tissues have characteristic mucin ‘expression profiles’. Mucins from rat small intestine occurred as an ‘insoluble glycoprotein complex’. The complex was composed of disulphide-bonded subunits containing two highly glycosylated mucin domains. The latter were of different length but substituted with similar oligosaccharides. Most of the neutral and sialic acid-containing glycans were relatively short and ‘simple’ structures. The human colonic ‘insoluble glycoprotein complex’ was shown the be mainly composed of MUC2 and virtually all MUC2 was present in this form. In addition to disulphide bonds, a ‘novel’ reduction-insensitive bond that joined subunits was iden-tified. Proteolytic cleavage in the C-terminal end of MUC2 occurred, leaving a 120 kDa fragment attached to the complex through disulphide bonds. A high-molecular-mass, monomeric, mucin with a high turnover-rate and high density was identified in colonic tissue incubated with radiolabelled mucin precursors. Most of the radiolabel was incorporated into this mucin while MUC2 was only poorly labelled. The presence of the monomeric mucin may complicate interpretations of metabolic studies designed to examine MUC2. Changes in the glycosylation of MUC2 was identified in colorectal carcinoma, including variations in blood group A, Lea, Leb, as well as Tn, sialyl-Tn, sialyl-Lea, sialyl-Lex antigen expression. However, an increased expression of the sialyl-Tn was the only finding consistently observed in tumour tissue. The various glycoproteins that form the basis for mucosal protection are very large and complex structures that so far have been difficult to isolate and study. Consequently, the progress of this particular niche of ‘matrix biology’ – focused on the interface between the outside and the inside of the body – has been hampered by a ‘methodological burden’. The work described here adds significantly to the information on the structure and properties of some of the major players in this field and also provides novel methodological approaches. Such work is a prerequisite for understanding pathological conditions characterised by a deranged mucosal protection and thus for the development of future approaches for handling such conditions.