Secretion of immunoglobulin M assembly intermediates in the presence of reducing agents

Cristina M. Alberini, Paola Bet, Cesar Milstein, Roberto Sitia

Research output: Contribution to journalArticle

Abstract

THERE are several demonstrations that misfolded or unassembled proteins are not transported along the secretory pathway, but are retained intracellularly, generally in the endoplasmic reticulum (reviewed in ref. 1). For instance, B lymphocytes synthesize but do not secrete IgM, and only the polymeric form of IgM is secreted by plasma cells. The C-terminal cysteine of the μ heavy chain of secreted IgM (residue 575) is involved in the intracellular retention of unpolymerized IgM subunits2. Here we report that the addition of reducing agents to the culture medium, at concentrations which do not affect cell viability, terminal glycosylation, or retention of proteins in the endoplasmic reticulum through the KDEL mechanism3, induces secretion of IgM assembly intermediates by both B and plasma cells. Free joining (J) chains, which are not normally secreted by plasma cells unless as part of IgM or IgA4, are also secreted in the presence of reducing agents. We propose a role for free thiol groups in preventing the unhindered transport of proteins through the secretory pathway. Under the scheme, assembly intermediates interact through their thiol groups between themselves and/or with unknown proteins of the endoplasmic reticulum. Such interactions may be prevented by altering the intracellular redox potential or by site-directed mutagenesis of the relevant cysteine residue(s).

Original languageEnglish
Pages (from-to)485-487
Number of pages3
JournalNature
Volume347
Issue number6292
Publication statusPublished - Oct 4 1990

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Reducing Agents
Immunoglobulin M
Plasma Cells
Endoplasmic Reticulum
Secretory Pathway
Sulfhydryl Compounds
Cysteine
B-Lymphocytes
Proteins
Site-Directed Mutagenesis
Glycosylation
Oxidation-Reduction
Culture Media
Cell Survival
Carrier Proteins

ASJC Scopus subject areas

  • General

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Alberini, C. M., Bet, P., Milstein, C., & Sitia, R. (1990). Secretion of immunoglobulin M assembly intermediates in the presence of reducing agents. Nature, 347(6292), 485-487.

Secretion of immunoglobulin M assembly intermediates in the presence of reducing agents. / Alberini, Cristina M.; Bet, Paola; Milstein, Cesar; Sitia, Roberto.

In: Nature, Vol. 347, No. 6292, 04.10.1990, p. 485-487.

Research output: Contribution to journalArticle

Alberini, CM, Bet, P, Milstein, C & Sitia, R 1990, 'Secretion of immunoglobulin M assembly intermediates in the presence of reducing agents', Nature, vol. 347, no. 6292, pp. 485-487.
Alberini, Cristina M. ; Bet, Paola ; Milstein, Cesar ; Sitia, Roberto. / Secretion of immunoglobulin M assembly intermediates in the presence of reducing agents. In: Nature. 1990 ; Vol. 347, No. 6292. pp. 485-487.
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