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Title

Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes
Authors
Piguet, Vincent
Gu, Feng
Foti, Michelangelo
Demaurex, Nicolas
Gruenberg, Jean
Carpentier, Jean-Louis
Trono, Didier
Published in Cell. 1999, vol. 97, no. 1, p. 63-73
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
Identifiers
PMID: 10199403
Full text
Article (Published version) (390 Kb) - public document Free access
Structures
Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire
Research groups Obésité et syndrome métabolique (803)
Signaux intracellulaires (210)
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. https://archive-ouverte.unige.ch/unige:30336

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Deposited on : 2013-10-11

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