Regulation of protein expression in differentiation by subunit assembly. Human membrane and secreted IgM.
Newly synthesized IgM heavy chains are either expressed as functional IgM or catabolized, depending on the stage of differentiation of the B cell. Heavy chains of the membrane type are rapidly degraded in pre-B cells, but expressed on the cell surface as monomeric IgM in resting and secreting B cells. Secreted-type heavy chains are catabolized in pre-B and resting B cells, but secreted as pentameric IgM by secreting B cells. The differences between the heavy chains that are expressed and those that are catabolized are post-translational. Stable membrane and secreted heavy chains have been covalently assembled with light chains, terminally glycosylated, and removed from intracellular proteases by insertion into the plasma membrane or by secretion. The carboxylic ionophores monensin and nigericin have been used here to determine the relative importance of these post-translational events in stabilizing newly synthesized heavy chains. Monensin and nigericin inhibited both the rates and extents of terminal glycosylation and of intracellular transport of these proteins, without affecting the covalent assembly processes. These ionophores did not affect the rate of catabolism of heavy chains in either a resting or a secreting B cell line. IgM heavy chains thus appear to be stabilized against intracellular proteolysis by full covalent assembly to monomeric membrane IgM and to secreted pentameric IgM. The fully assembled IgM can then be terminally glycosylated and transported to the cell surface.
D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis*; D046911:Macromolecular Substances; D008985:Monensin / Q000494:pharmacology; D009550:Nigericin / Q000494:pharmacology; D011499:Protein Processing, Post-Translational
D007075:Immunoglobulin M; D046911:Macromolecular Substances; D008985:Monensin; D009550:Nigericin