ERp44 and ERGIC-53 Synergize in Coupling Efficiency and Fidelity of IgM Polymerization and Secretion

被引:43
作者
Cortini, Margherita [1 ]
Sitia, Roberto [1 ]
机构
[1] Univ Vita Salute, Div Genet & Cell Biol, San Raffaele Sci Inst, I-20132 Milan, Italy
关键词
disulphide bonds; endoplasmic reticulum; glycosylation; protein folding; quality control; HIGH-MANNOSE OLIGOSACCHARIDES; ENDOPLASMIC-RETICULUM; QUALITY-CONTROL; IMMUNOGLOBULIN-M; LECTIN ERGIC-53; MYELOMA PROTEIN; B-CELLS; CHAIN; RETENTION; EXPRESSION;
D O I
10.1111/j.1600-0854.2010.01043.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 mu (mu(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 mu(s) tailpiece (mu(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 mu(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.
引用
收藏
页码:651 / 659
页数:9
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