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, antibodysecreting cells can release up to thousands of IgM per second. The finding that secretory μ (μs) 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 μs tailpiece (μstp). 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 μstp, 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.
ERp44 and ERGIC-53 Synergize in Coupling Efficiency and Fidelity of IgM Polymerization and Secretion
CORTINI M;
2010
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, antibodysecreting cells can release up to thousands of IgM per second. The finding that secretory μ (μs) 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 μs tailpiece (μstp). 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 μstp, 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
