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Scientific article
Open access
English

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

Published inCell, vol. 97, no. 1, p. 63-73
Publication date1999
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
  • Amino Acid Sequence
  • Animals
  • Antigens, CD4/metabolism
  • Binding Sites/physiology
  • CHO Cells
  • Cell Line
  • Coatomer Protein
  • Cricetinae
  • Dipeptides/physiology
  • Down-Regulation/physiology
  • Endosomes/metabolism/physiology
  • Gene Products, nef/physiology
  • HIV-1/physiology
  • Humans
  • Hydrogen-Ion Concentration
  • Kidney
  • Lysosomes/metabolism/physiology
  • Microtubule-Associated Proteins/metabolism/physiology
  • Molecular Sequence Data
  • Signal Transduction/physiology
  • Nef Gene Products, Human Immunodeficiency Virus
Citation (ISO format)
PIGUET, Vincent et al. Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes. In: Cell, 1999, vol. 97, n° 1, p. 63–73.
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Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0092-8674
547views
193downloads

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