The SH3 domain-binding surface and an acidic motif in HIV-1 Nef regulate trafficking of class I MHC complexes - PubMed (original) (raw)

The SH3 domain-binding surface and an acidic motif in HIV-1 Nef regulate trafficking of class I MHC complexes

M E Greenberg et al. EMBO J. 1998.

Abstract

Nef, a regulatory protein of human and simian immunodeficiency viruses, downregulates cell surface expression of both class I MHC and CD4 molecules in T cells by accelerating their endocytosis. Fibroblasts were used to study alterations in the traffic of class I MHC complexes induced by Nef. We found that Nef downregulates class I MHC complexes by a novel mechanism involving the accumulation of endocytosed class I MHC in the trans-Golgi, where it colocalizes with the adaptor protein-1 complex (AP-1). This effect of Nef on class I MHC traffic requires the SH3 domain-binding surface and a cluster of acidic amino acid residues in Nef, both of which are also required for Nef to downregulate class I MHC surface expression and to alter signal transduction in T cells. Downregulation of class I MHC complexes from the surface of T cells also requires a tyrosine residue in the cytoplasmic domain of the class I MHC heavy chain molecule. The requirement of the same surfaces of the Nef molecule for downregulation of surface class I MHC complexes in T cells and for their accumulation in the trans-Golgi of fibroblasts indicates that the two effects of Nef involve similar interactions with the host cell machinery and involve a molecular mechanism regulating class I MHC traffic that is common for both of these cell types. Interestingly, the downregulation of class I MHC does not require the ability of Nef to colocalize with the adaptor protein-2 complex (AP-2). We showed previously that the ability of Nef to colocalize with AP-2 correlates with the ability of Nef to downregulate CD4 expression. Our observations indicate that Nef downregulates class I MHC and CD4 surface expression via different interactions with the protein sorting machinery, and link the sorting and signal transduction machineries in the regulation of class I MHC surface expression by Nef.

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References

    1. J Exp Med. 1994 Jan 1;179(1):101-13 - PubMed
    1. J Biol Chem. 1993 Oct 25;268(30):22552-6 - PubMed
    1. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2688-92 - PubMed
    1. J Virol. 1995 Jan;69(1):528-33 - PubMed
    1. Annu Rev Immunol. 1996;14:369-96 - PubMed

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