A high-molecular-weight complex of membrane proteins BAP29/BAP31 is involved in the retention of membrane-bound IgD in the endoplasmic reticulum.
B cell antigen receptors (BCRs) are multimeric transmembrane protein complexes comprising membrane-bound immunoglobulins (mIgs) and Ig-alpha/Ig-beta heterodimers. In most cases, transport of mIgs from the endoplasmic reticulum (ER) to the cell surface requires assembly with the Ig-alpha/Ig-beta subunits. In addition to Ig-alpha/Ig-beta, mIg molecules also bind two ER-resident membrane proteins, ... BAP29 and BAP31, and the chaperone heavy chain binding protein (BiP). In this article, we show that neither Ig-alpha/Ig-beta nor BAP29/BAP31 nor BiP bind simultaneously to the same mIgD molecule. Blue native PAGE revealed that only a minor fraction of intracellular mIgD is associated with high-molecular-weight BAP29/BAP31 complexes. BAP-binding to mIgs was found to correlate with ER retention of chimeric mIgD molecules. On high-level expression in Drosophila melanogaster S2 cells, mIgD molecules were detected on the cell surface in the absence of Ig-alpha/Ig-beta. This aberrant transport was prevented by coexpression of BAP29 and BAP31. Thus, BAP complexes contribute to ER retention of mIg complexes that are not bound to Ig-alpha/Ig-beta. Furthermore, the mechanism of ER retention of both BAP31 and mIgD is not through retrieval from a post-ER compartment, but true ER retention. In conclusion, BAP29 and BAP31 might be the long sought after retention proteins and/or chaperones that act on transmembrane regions of various proteins.
Mesh Terms:
Animals, Antigens, CD, Antigens, CD79, Binding Sites, CHO Cells, COS Cells, Cell Line, Cricetinae, Dimerization, Drosophila melanogaster, Endoplasmic Reticulum, Immunoglobulin D, Intracellular Membranes, Macromolecular Substances, Membrane Proteins, Mice, Molecular Weight, Receptors, Antigen, B-Cell, Recombinant Fusion Proteins
Animals, Antigens, CD, Antigens, CD79, Binding Sites, CHO Cells, COS Cells, Cell Line, Cricetinae, Dimerization, Drosophila melanogaster, Endoplasmic Reticulum, Immunoglobulin D, Intracellular Membranes, Macromolecular Substances, Membrane Proteins, Mice, Molecular Weight, Receptors, Antigen, B-Cell, Recombinant Fusion Proteins
Proc. Natl. Acad. Sci. U.S.A.
Date: Aug. 19, 2003
PubMed ID: 12886015
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