ERp44 and ERGIC-53 synergize in coupling efficiency and fidelity of IgM polymerization and secretion

Margherita Cortini, Roberto Sitia

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)651-659
Number of pages9
JournalTraffic
Volume11
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • Disulphide bonds
  • Endoplasmic reticulum
  • Glycosylation
  • Protein folding
  • Quality control

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

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