TY - JOUR
T1 - Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class i molecules
AU - Howe, Christopher
AU - Garstka, Malgorzata
AU - Al-Balushi, Mohammed
AU - Ghanem, Esther
AU - Antoniou, Antony N.
AU - Fritzsche, Susanne
AU - Jankevicius, Gytis
AU - Kontouli, Nasia
AU - Schneeweiss, Clemens
AU - Williams, Anthony
AU - Elliott, Tim
AU - Springer, Sebastian
PY - 2009/12
Y1 - 2009/12
N2 - Calreticulin is a lectin chaperone of the endoplasmic reticulum (ER). In calreticulin-deficient cells, major histocompatibility complex (MHC) class I molecules travel to the cell surface in association with a sub-optimal peptide load. Here, we show that calreticulin exits the ER to accumulate in the ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi, together with sub-optimally loaded class I molecules. Calreticulin that lacks its C-terminal KDEL retrieval sequence assembles with the peptide-loading complex but neither retrieves sub-optimally loaded class I molecules from the cis-Golgi to the ER, nor supports optimal peptide loading. Our study, to the best of our knowledge, demonstrates for the first time a functional role of intracellular transport in the optimal loading of MHC class I molecules with antigenic peptide.
AB - Calreticulin is a lectin chaperone of the endoplasmic reticulum (ER). In calreticulin-deficient cells, major histocompatibility complex (MHC) class I molecules travel to the cell surface in association with a sub-optimal peptide load. Here, we show that calreticulin exits the ER to accumulate in the ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi, together with sub-optimally loaded class I molecules. Calreticulin that lacks its C-terminal KDEL retrieval sequence assembles with the peptide-loading complex but neither retrieves sub-optimally loaded class I molecules from the cis-Golgi to the ER, nor supports optimal peptide loading. Our study, to the best of our knowledge, demonstrates for the first time a functional role of intracellular transport in the optimal loading of MHC class I molecules with antigenic peptide.
KW - Calreticulin
KW - Endoplasmic reticulum
KW - Major histocompatibility complex (MHC) class I molecules
KW - Peptides
KW - Quality control
UR - http://www.scopus.com/inward/record.url?scp=71349084487&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71349084487&partnerID=8YFLogxK
U2 - 10.1038/emboj.2009.296
DO - 10.1038/emboj.2009.296
M3 - Article
C2 - 19851281
AN - SCOPUS:71349084487
SN - 0261-4189
VL - 28
SP - 3730
EP - 3744
JO - EMBO Journal
JF - EMBO Journal
IS - 23
ER -