Nef Interacts with the μ Subunit of Clathrin Adaptor Complexes and Reveals a Cryptic Sorting Signal in MHC I Molecules

• Published in: Immunity (Cambridge, Mass.) Mass.), 1998-04, Vol.8 (4), p.483-495
• Main Authors: Le Gall, Sylvie, Erdtmann, Lars, Benichou, Serge, Berlioz-Torrent, Clarisse, Liu, Langxia, Benarous, Richard, Heard, Jean-Michel, Schwartz, Olivier
• Format: Article
• Language: English
• Subjects: Adaptor Protein Complex alpha Subunits; Adaptor Proteins, Vesicular Transport; AIDS/HIV; Amino Acid Sequence; Binding Sites; CD4 Antigens - metabolism; Clathrin - chemistry; Clathrin - metabolism; Down-Regulation; Gene Products, nef - metabolism; HeLa Cells; HIV Infections - metabolism; HIV-1 - metabolism; HIV-2 - metabolism; HLA-A Antigens - chemistry; HLA-A Antigens - genetics; HLA-A Antigens - metabolism; HLA-B Antigens - chemistry; HLA-B Antigens - genetics; HLA-B Antigens - metabolism; HLA-C Antigens - chemistry; HLA-C Antigens - genetics; HLA-C Antigens - metabolism; Humans; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Models, Biological; Molecular Sequence Data; nef Gene Products, Human Immunodeficiency Virus; Protein Conformation; Signal Transduction; Simian Immunodeficiency Virus - metabolism
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80553-1

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 (μ) 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.