Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes.

Cell. 1999 Apr 2;97(1):63-73. Unique Identifier : AIDSLINE MED/99213495
Piguet V; Gu F; Foti M; Demaurex N; Gruenberg J; Carpentier JL; Trono D; Department of Genetics, Faculty of Medicine, University of; Geneva, Switzerland.

Abstract: The Nef protein of primate lentiviruses downregulates the cell surface expression of CD4 through a two-step process. First, Nef connects the cytoplasmic tail of CD4 with adaptor protein complexes (AP), thereby inducing the formation of CD4-specific clathrin-coated pits that rapidly endocytose the viral receptor. Second, Nef targets internalized CD4 molecules for degradation. Here we show that Nef accomplishes this second task by acting as a connector between CD4 and the beta subunit of COPI coatomers in endosomes. A sequence encompassing a critical acidic dipeptide, located nearby but distinct from the AP-binding determinant of HIV-1 Nef, is responsible for beta-COP recruitment and for routing to lysosomes. A novel class of endosomal sorting motif, based on acidic residues, is thus revealed, and beta-COP is identified as its downstream partner.

Keywords: JOURNAL ARTICLE Amino Acid Sequence Animal Antigens, CD4/*METABOLISM Binding Sites/PHYSIOLOGY Cell Line CHO Cells Dipeptides/PHYSIOLOGY Down-Regulation (Physiology)/PHYSIOLOGY Endosomes/*METABOLISM/PHYSIOLOGY Gene Products, nef/*PHYSIOLOGY Hamsters Human Hydrogen-Ion Concentration HIV-1/*PHYSIOLOGY Kidney Lysosomes/METABOLISM/*PHYSIOLOGY Microtubule-Associated Proteins/*METABOLISM/PHYSIOLOGY Molecular Sequence Data Signal Transduction/*PHYSIOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S.
990730
A9971172

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