title: ERp44 and ERGIC-53 synergize in coupling efficiency and fidelity of IgM polymerization and secretion.
abstract: Owing to the quality control mechanisms operating in the early secretory compartment, only native proteins are secreted. Despite the difficulties in assembling planar immunoglobulin M (IgM) polymers, antibody-secreting cells can release up to thousands of IgM per second. The finding that secretory micro (micro(s)) chains bind to ERGIC-53, a lectin transporter that cycles in the early secretory compartment, suggested that ERGIC-53 hexamers could provide a polymerization platform. Here,we show that ERGIC-53 binds to the conserved Asn563 glycan in the C-terminal micro(s) tailpiece (micro(s)tp). Removal of this glycan inhibits ERGIC-53 binding and results in the rapid formation of larger polymeric assemblies. In contrast, removal of the Asn402 oligosaccharides prevents both polymerization and secretion. ERp44,a chaperone that interacts with ERGIC-53, binds to Cys575 in the micro(s)tp, providing a fail-safe mechanism that retrieves unpolymerized IgM subunits and promotes polymerization. The coordinated action of ERGIC-53 and ERp44 provides a way to improve the efficiency of IgM secretion without perturbing its fidelity.
authors.affiliation: Universita' Vita-Salute, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina 58, Milano, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Cortini
authors.forename: Roberto
authors.initials: R
authors.lastname: Sitia
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D011506:Proteins / Q000378:metabolism
chemical_list: D007075:Immunoglobulin M; D018832:Molecular Chaperones; D011108:Polymers; D011134:Polysaccharides; D011506:Proteins