IgM polymerization inhibits the Golgi-mediated processing of the mu-chain carboxy-terminal glycans.
Secreted glycoproteins generally contain oligosaccharides of the complex type. However, several molecules have been described in which individual glycans are processed differently from one another. Folding, assembly and oligomerization could affect the maturation of certain glycans by hindering them to the Golgi processing machinery. We have tested this possibility by analysing a panel of engineered murine mu chains secreted as mu2L2 monomers or as polymers, and having or not the carboxy-terminal glycan (Asn563). In secreted IgM polymers, Asn563 bears high-mannose oligosaccharides, typical of endoplasmic reticulum resident proteins, while complex sugars are found at the other four sites (Brenckle and Kornfeld, 1980 Arch. Biochem. Biophys. 243, 605-618). Polymeric and monomeric IgM contain mu chains whose glycans are processed differently. We show here that this is mainly due to the differential processing at the Asn563 glycan, which undergoes Golgi-mediated processing when IgM are secreted in the monomeric form. These results indicate that the oligomerization-dependent accessibility to the sugar modifying enzymes can be one of the key features that dictate the extent of oligosaccharide processing in multimeric glycoproteins. The presence of high mannose glycans at Asn563 implies that IgM polymerization takes place before encountering mannosidase II, likely in a pre-Golgi compartment.
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DIBIT San Raffaele Scientific Institute, 20132 Milano, Italy.
Guenzi
S
S
Carelli
S
S
Simmen
T
T
Sparvoli
A
A
Sitia
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001216:Asparagine / Q000737:chemistry; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism*; D007148:Immunoglobulin mu-Chains / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011108:Polymers; D011134:Polysaccharides / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D011108:Polymers; D011134:Polysaccharides; C024242:polymeric IgM; D001216:Asparagine