Nef interacts with the mu subunit of clathrin adaptor complexes and reveals a cryptic sorting signal in MHC I molecules.
The surface expression of MHC I is reduced in HIV-infected cells. We show that the Nef protein affects the intracellular sorting of HLA-A and -B molecules. In the presence of Nef, these proteins accumulate in the Golgi and colocalize with clathrin-coated vesicles. MHC I modulation relies on a tyrosine-based sorting signal located in the cytoplasmic domain of HLA-A and -B heavy chains. This cryptic sorting signal becomes operative only in the presence of Nef. Nef interacts with the medium (mu) subunit of AP adaptor complexes involved in the recognition of tyrosine-based sorting signals, likely facilitating the connection between MHC I and the clathrin-dependent sorting machinery.
Le Gall
S
S
Laboratoire Rétrovirus et Transfert Génétique Unité de Recherche Associée CNRS 1157, Institut Pasteur, Paris, France.
Erdtmann
L
L
Benichou
S
S
Berlioz-Torrent
C
C
Liu
L
L
Benarous
R
R
Heard
J M
JM
Schwartz
O
O
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D002966:Clathrin / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation; D015693:Gene Products, nef / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D015498:HIV-2 / Q000378:metabolism; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015235:HLA-B Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015236:HLA-C Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D011487:Protein Conformation; D015398:Signal Transduction; D015302:Simian Immunodeficiency Virus / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D015704:CD4 Antigens; D002966:Clathrin; D015693:Gene Products, nef; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D008565:Membrane Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus