Efficient IgM assembly and secretion require the plasma cell induced endoplasmic reticulum protein pERp1.
Plasma cells daily secrete their own mass in antibodies, which fold and assemble in the endoplasmic reticulum (ER). To reach these levels, cells require pERp1, a novel lymphocyte-specific small ER-resident protein, which attains expression levels as high as BiP when B cells differentiate into plasma cells. Although pERp1 has no homology with known ER proteins, it does contain a CXXC motif typical for oxidoreductases. In steady state, the CXXC cysteines are locked by two parallel disulfide bonds with a downstream C(X)(6)C motif, and pERp1 displays only modest oxidoreductase activity. pERp1 emerged as a dedicated folding factor for IgM, associating with both heavy and light chains and promoting assembly and secretion of mature IgM.
van Anken
Eelco
E
Cellular Protein Chemistry and Biomolecular Mass Spectrometry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
Pena
Florentina
F
Hafkemeijer
Nicole
N
Christis
Chantal
C
Romijn
Edwin P
EP
Grauschopf
Ulla
U
Oorschot
Viola M J
VM
Pertel
Thomas
T
Engels
Sander
S
Ora
Ari
A
Lástun
Viorica
V
Glockshuber
Rudi
R
Klumperman
Judith
J
Heck
Albert J R
AJ
Luban
Jeremy
J
Braakman
Ineke
I
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000648:ultrastructure; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007075:Immunoglobulin M / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007075:Immunoglobulin M; D018832:Molecular Chaperones; D013438:Sulfhydryl Compounds; D010088:Oxidoreductases