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

作者：Cortini Margherita; Sitia Roberto^*

来源：Traffic, 2010, 11(5): 651-659.

DOI：10.1111/j.1600-0854.2010.01043.x

• disulphide bonds
• endoplasmic reticulum
• glycosylation
• protein folding
• quality control

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.

• 出版日期2010-5