Sequential steps and checkpoints in the early exocytic compartment during secretory IgM biogenesis |
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Authors: | Anelli Tiziana Ceppi Stefania Bergamelli Leda Cortini Margherita Masciarelli Silvia Valetti Caterina Sitia Roberto |
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Affiliation: | Università Vita-Salute, San Raffaele Scientific Institute, Milano, Italy. |
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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. |
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Keywords: | endoplasmic reticulum ERGIC IgM protein folding quality control |
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