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. 1994 Jul 1;180(1):407–412. doi: 10.1084/jem.180.1.407

Calnexin retains unassembled major histocompatibility complex class I free heavy chains in the endoplasmic reticulum

PMCID: PMC2191536  PMID: 8006598

Abstract

The assembly of major histocompatibility complex (MHC) class I molecules involves the association of heavy (H) chain with beta 2- microglobulin (beta 2m) and peptide. Unassembled class I H chains do not exit the endoplasmic reticulum (ER) and this is exemplified by the beta 2m-deficient human melanoma FO-1 where free class I H chains are unable to complete assembly. In pulse chase experiments involving FO-1 cells, unassembled free class I H chains were shown to be stably associated with calnexin (IP90/p88), a 90-kD integral membrane molecular chaperone of the ER. To establish a role for calnexin in mediating this retention, we transfected FO-1 cells with a cytoplasmic tail deletion mutant of calnexin. Since the cytoplasmic tail contains the ER retention motif, these mutant calnexin molecules leave the ER and progress to the cell surface. In these stable transfectants of FO- 1, free class I H chains also exited the ER and trafficked to the cell surface with calnexin, thus establishing a role for calnexin in the quality control of MHC class I assembly through mediating the ER retention of incompletely assembled class I H chains.

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Selected References

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