Retention of unassembled components of integral membrane proteins by calnexin.
Quality control mechanisms prevent the cell surface expression of incompletely assembled multisubunit receptors such as the T cell receptor (TCR). The molecular chaperone function of calnexin (IP90, p88), a 90-kilodalton protein that resides in the endoplasmic reticulum (ER), in the retention of representative chains of the TCR-CD3 complex in the ER was tested. Truncation mutants of calnexin, when transiently expressed in COS cells, were exported from the ER and either accumulated in the Golgi or progressed to the cell surface. CD3 epsilon chains cotransfected with the forms of calnexin that were not retained in the ER exited the ER and colocalized with calnexin. Since engineered calnexin determined the intracellular localization of the proteins associated with it, it is concluded that calnexin interacts with incompletely assembled TCR components and retains them in the ER.
Rajagopalan
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S
Department of Rheumatology and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Xu
Y
Y
Brenner
M B
MB
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017252:CD3 Complex / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D037281:Calnexin; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D017252:CD3 Complex; D002135:Calcium-Binding Proteins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011994:Recombinant Proteins; D037281:Calnexin