title: Sequential steps and checkpoints in the early exocytic compartment during secretory IgM biogenesis.
abstract: The biogenesis of secretory IgM occurs stepwise under stringent quality control, formation of micro(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 micro(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, micro chains interact first with BiP and later with ERp44 and ERGIC-53. Our findings suggest that ERGIC-53 provides a platform that receives micro(2)L(2) subunits from the BiP-dependent checkpoint, assisting polymerization. In this process, ERp44 couples thiol-dependent assembly and quality control.
authors.affiliation: Università Vita-Salute, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Anelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Ceppi
authors.forename: Leda
authors.initials: L
authors.lastname: Bergamelli
authors.forename: Margherita
authors.initials: M
authors.lastname: Cortini
authors.forename: Silvia
authors.initials: S
authors.lastname: Masciarelli
authors.forename: Caterina
authors.initials: C
authors.lastname: Valetti
authors.forename: Roberto
authors.initials: R
authors.lastname: Sitia
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D020868:Gene Silencing; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis* / Q000235:genetics; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*