Expression of major histocompatibility complex class II molecules in HeLa cells promotes the recruitment of AP-1 Golgi-specific assembly proteins on Golgi membranes.
The newly synthesized major histocompatibility complex (MHC) class II molecules, an alphabeta dimer associated with the Ii invariant chain, must be targeted to endosomal, lysosomal enzyme-rich compartments in order to bind and present immunogenic peptides. The precise route followed by this complex at the exit of the trans-Golgi network, the last sorting station of the biosynthetic pathway, is poorly understood. We show here that overexpression of alphabetaIi complexes in HeLa cells promotes the first step of clathrin-coat assembly in vitro, that is the ARF-dependent translocation of AP-1 Golgi-specific assembly proteins on membranes. In contrast, alphabeta dimers alone or associated with Ii lacking most of its cytoplasmic domain fail to recruit AP-1. This study strongly suggests that the invariant chain (Ii) is responsible for the AP-1-dependent sorting of the alphabeta dimers in the trans-Golgi network of HeLa cells and that the MHC class II molecules are, like the mannose 6-phosphate receptors, transported directly from this compartment to endosomes via clathrin-coated vesicles.
Salamero
J
J
UMR 144 CNRS- Institut Curie, Laboratoire "Mecanismes Moléculaires du Transport Intracellulaire, 12 rue Lhomond, 75005 Paris, France.
Le Borgne
R
R
Saudrais
C
C
Goud
B
B
Hoflack
B
B
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001692:Biological Transport; D002451:Cell Compartmentation; D006056:Golgi Apparatus / Q000378:metabolism*; D006681:HLA-D Antigens / Q000378:metabolism*; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000944:Antigens, Differentiation, B-Lymphocyte; D006681:HLA-D Antigens; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C045084:invariant chain