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Sequential steps and checkpoints in the early exocytic compartment during secretory IgM biogenesis
Author(s) -
Anelli Tiziana,
Ceppi Stefania,
Bergamelli Leda,
Cortini Margherita,
Masciarelli Silvia,
Valetti Caterina,
Sitia Roberto
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601844
Subject(s) - biology , biogenesis , compartment (ship) , microbiology and biotechnology , genetics , gene , geology , oceanography
The biogenesis of secretory IgM occurs stepwise under stringent quality control, formation of μ 2 L 2 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 μ 2 L 2 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 μ 2 L 2 subunits from the BiP‐dependent checkpoint, assisting polymerization. In this process, ERp44 couples thiol‐dependent assembly and quality control.