Sequential steps and checkpoints in the early exocytic compartment during secretory IgM biogenesis

Silvia Masciarelli, Tiziana Anelli, Stefania Ceppi, Leda Bergamelli, Margherita Cortini, Caterina Valetti, Roberto Sitia

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

The biogenesis of secretory IgM occurs stepwise under stringent quality control, formation of μ2L2 preceding polymerization. How is efficiency of IgM secretion coupled to fidelity? We show here that ERp44, a soluble protein involved in thiol-mediated retention, interacts with ERGIC-53. Binding to this hexameric lectin contributes to ERp44 localization in the ER-golgi intermediate compartment. ERp44 and ERGIC-53 increase during B-lymphocyte differentiation, concomitantly with the onset of IgM polymerization. Both preferentially bind μ2L2 and higher order intermediates. Their overexpression or silencing in non-lymphoid cells promotes or decreases secretion of IgM polymers, respectively. In IgM-secreting B-lymphoma cells, μ chains interact first with BiP and later with ERp44 and ERGIC-53. Our findings suggest that ERGIC-53 provides a platform that receives μ2L2 subunits from the BiP-dependent checkpoint, assisting polymerization. In this process, ERp44 couples thiol-dependent assembly and quality control. © 2007 European Molecular Biology Organization | All Rights Reserved.
Original languageEnglish
Pages (from-to)4177-4188
Number of pages12
JournalEMBO Journal
Volume26
DOIs
Publication statusPublished - 2007

Keywords

  • B-Lymphocytes
  • ERGIC
  • Endoplasmic Reticulum
  • Endoplasmic reticulum
  • Gene Silencing
  • Golgi Apparatus
  • HeLa Cells
  • Heat-Shock Proteins
  • Humans
  • IgM
  • Immunoglobulin Light Chains
  • Immunoglobulin mu-Chains
  • Mannose-Binding Lectins
  • Membrane Proteins
  • Molecular Chaperones
  • Protein folding
  • Quality control

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