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.
Schamel
Wolfgang W A
WW
Department of Molecular Immunology, Biology III, University of Freiburg and Max-Planck-Institut für Immunobiologie, D-79108 Freiburg, Germany.
Kuppig
Stephan
S
Becker
Bernd
B
Gimborn
Kerstin
K
Hauri
Hans-Peter
HP
Reth
Michael
M
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001665:Binding Sites; D051925:CD79 Antigens; D016466:CHO Cells; D019556:COS Cells; D002460:Cell Line; D006224:Cricetinae; D019281:Dimerization; D004331:Drosophila melanogaster; D004721:Endoplasmic Reticulum / Q000276:immunology* / Q000378:metabolism*; D007072:Immunoglobulin D / Q000737:chemistry / Q000378:metabolism*; D007425:Intracellular Membranes / Q000276:immunology / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; C486244:BCAP29 protein, human; C489641:Bcap29 protein, mouse; C489642:Bcap31 protein, mouse; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; D007072:Immunoglobulin D; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins