Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain.
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Aiken C, Konner J, Landau NR, Lenburg ME, Trono D
Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain.
Cell. 1994 Mar 11;76(5):853-64.
- PubMed ID
- 8124721 [ View in PubMed]
- Abstract
CD4 is crucial for antigen-driven helper T cell signaling and is used as receptor by the human immunodeficiency virus (HIV). The HIV early protein Nef causes a loss of CD4 from cell surfaces through a previously undefined posttranscriptional mechanism. Here, we demonstrate that Nef acts by inducing CD4 endocytosis, resulting in its degradation in lysosomes. CD4 down-regulation is strongly enhanced by the association of Nef with cell membranes through myristoylation. The study of chimeric molecules reveals that 20 membrane-proximal residues of the CD4 cytoplasmic domain are sufficient to confer Nef sensitivity. Within this region, a dileucine motif, reminiscent of an endocytosis and lysosomal targeting signal found in the CD3 gamma and delta chains, is crucial for CD4 response to Nef.