IGM POLYMERIZATION INHIBITS THE GOLGI-MEDIATED PROCESSING OF THE MU-CHAIN CARBOXY-TERMINAL GLYCANS

Secreted glycoproteins generally contain oligosaccharides of the compl ex type. However, several molecules have been described in which indiv idual glycans are processed differently from one another. Folding, ass embly and oligomerization could affect the maturation of certain glyca ns by hindering them to the Golgi processing machinery. We have tested this possibility by analysing a panel of engineered murine mu chains secreted as mu 2L2 monomers or as polymers, and having or not the carb oxy-terminal glycan (Asn563). In secreted IgM polymers, Asn563 bears h igh-mannose oligosaccharides, typical of endoplasmic reticulum residen t proteins, while complex sugars are found at the other four sites (Br enckle and Kornfeld, 1980 Arch. Biochem. Biophys. 243, 605-618). Polym eric and monomeric IgM contain mu chains whose glycans are processed d ifferently. We show here that this is mainly due to the differential p rocessing at the Asn563 glycan, which undergoes Golgi-mediated process ing when IgM are secreted in the monomeric form. These results indicat e that the oligomerization-dependent accessibility to the sugar modify ing enzymes can be one of the key features that dictate the extent of oligosaccharide processing in multimeric glycoproteins. The presence o f high mannose glycans at Asn563 implies that IgM polymerization takes place before encountering mannosidase II, likely in a pre-Golgi compa rtment.