HIV-1 Nef Disrupts Antigen Presentation Early in the Secretory Pathway
| Autor: | Kathleen L. Collins, Rebekah I. Fleis, Matthew R. Kasper, Maya Williams, Tracey Filzen, Jeremiah F. Roeth |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cytoplasm
Time Factors T-Lymphocytes viruses Molecular Sequence Data Antigen presentation Genes MHC Class I Golgi Apparatus chemical and pharmacologic phenomena Cell Separation Major histocompatibility complex Biochemistry Gene Products nef Adenoviridae Phosphates symbols.namesake HLA-A2 Antigen MHC class I Humans Immunoprecipitation Cytotoxic T cell Amino Acid Sequence Phosphorylation Molecular Biology Secretory pathway Antigen Presentation Sequence Homology Amino Acid biology Endoplasmic reticulum Cell Membrane Temperature virus diseases Signal transducing adaptor protein Biological Transport Cell Biology Golgi apparatus Flow Cytometry Cell biology Microscopy Fluorescence Mutation biology.protein symbols RNA Interference Lysosomes HeLa Cells Protein Binding trans-Golgi Network |
| Zdroj: | Journal of Biological Chemistry. 280:12840-12848 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m413538200 |
| Popis: | Human immunodeficiency virus, type 1 Nef disrupts viral antigen presentation and promotes viral immune evasion from cytotoxic T lymphocytes. There is evidence that Nef acts early in the secretory pathway to redirect major histocompatibility complex class I (MHC-I) from the trans-Golgi network to the endolysosomal pathway. However, a competing model suggests that Nef acts much later by accelerating MHC-I turnover at the cell surface. Here we demonstrate that Nef targets early forms of MHC-I molecules in the endoplasmic reticulum by preferentially binding hypophosphorylated cytoplasmic tails. The Nef-MHC-I complex migrates normally into the Golgi apparatus but subsequently fails to arrive at the cell surface and become phosphorylated. Cell type-specific differences in the rate of MHC-I transport through the secretory pathway correlate with responsiveness to Nef and co-precipitation of adaptor protein 1 with the Nef.MHC-I complex. We propose that the assembly of a Nef.MHC-I.adaptor protein 1 complex early in the secretory pathway is important for Nef activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|