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Mechanism of Nef‐induced CD4 endocytosis: Nef connects CD4 with the μ chain of adaptor complexes
Author(s) -
Piguet Vincent,
Chen YenLiang,
Mangasarian Aram,
Foti Michelangelo,
Carpentier JeanLouis,
Trono Didier
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.9.2472
Subject(s) - biology , signal transducing adaptor protein , endocytosis , mechanism (biology) , microbiology and biotechnology , chain (unit) , signal transduction , genetics , receptor , philosophy , physics , epistemology , astronomy
The Nef protein of primate lentiviruses down‐regulates the cell surface expression of CD4 and probably MHC I by connecting these receptors with the endocytic machinery. Here, we reveal that Nef interacts with the μ chains of adaptor complexes, key components of clathrin‐coated pits. For human immunodeficiency virus type 2 (HIV‐2) and simian immunodeficiency virus (SIV) Nef, this interaction occurs via tyrosine‐based motifs reminiscent of endocytosis signals. Mutating these motifs prevents the binding of SIV Nef to the μ chain of plasma membrane adaptor complexes, abrogates its ability to induce CD4 internalization, suppresses the accelerated endocytosis of a chimeric integral membrane protein harboring Nef as its cytoplasmic domain and confers a dominant‐negative phenotype to the viral protein. Taken together, these data identify μ adaptins as downstream mediators of the down‐modulation of CD4, and possibly MHC I, by Nef.