Immunoglobulin light chains dictate vesicular transport-dependent and -independent routes for IgM degradation by the ubiquitin-proteasome pathway.
Degradation of IgM mu heavy chains in light chain-negative pre-B cells is independent of vesicular transport, as is evident by its insensitivity to brefeldin A or cell permeabilization. Conversely, by the same criteria, degradation of the secretory mu heavy chain in light chain-expressing B cells depends on vesicular transport. To investigate whether the presence of conventional light chains or the developmental stage of the B-lymphocytes dictates the degradative route taken by mu, we express in 70Z/3 pre-B cells either lambda ectopically or kappa by lipopolysaccharides-stimulated differentiation into B cells and show their assembly with mu heavy chains. The resulting sensitivity of mu degradation to brefeldin A and cell permeabilization demonstrates that conventional light chains, a hallmark of B cell differentiation, are necessary and sufficient to divert mu from a vesicular transport-independent to a vesicular transport-dependent degradative route. Although both routes converge at the ubiquitin-proteasome degradation pathway, only in light chain-expressing cells is vesicular transport a prerequisite for mu ubiquitination.
Elkabetz
Yechiel
Y
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Kerem
Anat
A
Tencer
Lilach
L
Winitz
Dorit
D
Kopito
Ron R
RR
Bar-Nun
Shoshana
S
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000648:ultrastructure; D001692:Biological Transport; D020126:Brefeldin A / Q000494:pharmacology; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D015870:Gene Expression; D006360:Heat-Shock Proteins; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000502:physiology*; D007075:Immunoglobulin M / Q000378:metabolism*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000502:physiology; D007146:Immunoglobulin lambda-Chains / Q000235:genetics / Q000502:physiology; D007148:Immunoglobulin mu-Chains / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D014162:Transfection; D022161:Transport Vesicles / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D008070:Lipopolysaccharides; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D025801:Ubiquitin; D020126:Brefeldin A; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex