SERIES ON AIRWAYS SECRETIONS - NEW CONCEPTS AND FUNCTIONS Human respiratory mucins

For more than a century the concept of mucin was associated with material secreted in mucus. Mucins (including blood group substances), the main constituents of most mucus, were probably the first type of compounds to be clearly recognized as glycoproteins. However, the precise definition of mucins in general, as well as that of respiratory mucins, is still evolving due to the complexity of these molecules [1]. Initially, the definition of mucins was based on the chemical composition (from 50-80% carbohydrate) and molecular mass (from several hundred to several thousand kDa). In the typical chemical composition of human respiratory mucins, there is more than three times more carbohydrate than peptide. The proportion of hydroxylated amino acid is high (from 3~35 serine and threonine residues per 100 amino acid residues) as are the proportions of all the sugars usually found in mucins, i.e. fucose, galactose, N-acetylglucosamine, N-acetylgalactosamine, sialic acid. Respiratory mucins also contain sulphate but no uronic acid and perhaps a small quantity of mannose which will be discussed later. The physical polydispersity and several other lines of evidence clearly indicate that there is not a single mucin, such as a unique respiratory mucin, but a very large family of mucin molecules, differing from each other at the peptide and at the carbohydrate levels. In the present review, we will describe the evidence which suggests that human respiratory mucins are a broad family of different glycoproteins which seems to stem from two events, firstly the expression of mucin genes into multiple apomucins, then a diversity of posttranslational phenomena, mainly 0-glycosylation leading to carbohydrate chains with a vast microheterogeneity. We will also try to speculate on the possible biological significance of such a diversity.