The KDEL receptor mediates a retrieval mechanism that contributes to quality control at the endoplasmic reticulum.
Newly synthesized proteins in the endoplasmic reticulum (ER) must fold and assemble correctly before being transported to their final cellular destination. While some misfolded or partially assembled proteins have been shown to exit the ER, they fail to escape the early secretory system entirely, because they are retrieved from post-ER compartments to the ER. We elucidate a mechanistic basis for this retrieval and characterize its contribution to ER quality control by studying the fate of the unassembled T-cell antigen receptor (TCR) alpha chain. While the steady-state distribution of TCRalpha is in the ER, inhibition of retrograde transport by COPI induces the accumulation of TCRalpha in post-ER compartments, suggesting that TCRalpha is cycling between the ER and post-ER compartments. TCRalpha associates with BiP, a KDEL protein. Disruption of the ligand-binding function of the KDEL receptor releases TCRalpha from the early secretory system to the cell surface, so that TCRalpha is no longer subject to ER degradation. Thus, our findings suggest that retrieval by the KDEL receptor contributes to mechanisms by which the ER monitors newly synthesized proteins for their proper disposal.
Yamamoto
K
K
Department of Molecular Embryology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Fujii
R
R
Toyofuku
Y
Y
Saito
T
T
Koseki
H
H
Hsu
V W
VW
Aoe
T
T
D000818:Animals; D022181:COP-Coated Vesicles / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
C064459:KDEL receptor; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins