Fauré J Stalder R Borel C Sobo K Piguet V Demaurex N Gruenberg J Trono D 2004 BACKGROUND The HIV Nef protein downregulates CD4 through sequential connection with clathrin-coated pits and the COP1 coatomer, resulting in accelerated endocytosis and lysosomal targeting. RESULTS Here we report that the small GTPase ARF1 controls the Nef-induced, COP-mediated late-endosomal targeting of CD4. We find that Nef binds ARF1 directly and can recruit the GTPase onto endosomal membranes. Furthermore, a complex comprising Nef, ARF1, and betaCOP can be immunoprecipitated from cells expressing the viral protein. Residues in a C-terminal loop of the viral protein facilitate both these interactions and the targeting of Nef and CD4 to acidic late endosomes, whereas other residues primarily involved in mediating CD4 endocytosis are dispensable for this process. Finally, a dominant-negative ARF1 mutant blocks the migration of the Nef-CD4 complex to lysosomes. CONCLUSIONS Our results support a model in which ARF1 is the immediate downstream partner of Nef for CD4 lysosomal targeting. https://sonar.ch/global/documents/230496 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cub.2004.06.021 info:eu-repo/semantics/altIdentifier/pmid/15202998 Current biology : CB. - 2004 ADP-Ribosylation Factor 1 Animals CD4 Antigens Cells, Cultured Coated Pits, Cell-Membrane Cricetinae Endocytosis Endosomes Fluorescent Antibody Technique Gene Products, nef Genetic Vectors HIV HeLa Cells Humans Microscopy, Confocal Mutation Plasmids Precipitin Tests Ubiquitin-Protein Ligases Viral Fusion Proteins nef Gene Products, Human Immunodeficiency Virus ARF1 regulates Nef-induced CD4 degradation. http://purl.org/coar/resource_type/c_6501