Accelerated proteasomal degradation of membrane Ig heavy chains.
Membrane IgG H chains turn over considerably more rapidly than secretory Ig H chains in the 18-81 A2 pre-B cell line. This rapid degradation occurs in proteasomes. N-Glycosylated membrane Ig H chains accumulate in the endoplasmic reticulum in the presence of proteasomal inhibitors, suggesting that retrotranslocation and proteasomal degradation of membrane Ig H chains may be closely coupled processes. Accelerated proteasomal degradation of membrane Ig H chains was also observed in transfected nonlymphoid cells. At steady state, the membrane form of the H chain associates more readily with Bip and calnexin than its secretory counterpart. The preferential recognition of membrane, as opposed to secretory, Ig H chains by some endoplasmic reticulum chaperones, may provide an explanation for the accelerated proteasomal degradation of the former.
Ho
S C
SC
Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02129, USA.
Chaudhuri
S
S
Bachhawat
A
A
McDonald
K
K
Pillai
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000378:metabolism; D001692:Biological Transport / Q000276:immunology; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037281:Calnexin; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007142:Immunoglobulin gamma-Chains / Q000378:metabolism; D007212:Indolizines / Q000494:pharmacology; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000276:immunology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D054836:Indolizidines
D002135:Calcium-Binding Proteins; D037281:Calnexin; D002352:Carrier Proteins; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D007212:Indolizines; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D046988:Proteasome Endopeptidase Complex; D011947:Receptors, Antigen, B-Cell; C037806:castanospermine; D054836:Indolizidines