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Journal of Virology, March 2001, p. 2982-2992, Vol. 75, No. 6
Institute of Microbiology, University of
Lausanne, CH-1011 Lausanne, Switzerland1;
CJF 97/03 INSERM, Institut Cochin de Génétique
Moléculaire, 75014 Paris, France2;
Biochemistry II, University of Goettingen, 37073 Goettingen, Germany3; and Department of
Microbiology and Molecular Genetics, University of Vermont,
Burlington, Vermont 054054
Received 8 November 2000/Accepted 13 December 2000
Short amino acid sequences in the cytosolic domains of
transmembrane proteins are recognized by specialized adapter proteins which are part of coated vesicles utilized to transport membrane proteins between the trans-Golgi network (TGN) and the plasma membrane
(forward and backward). Previously, we and others
reported that the membrane-proximal tyrosine residues Y712 (human
immunodeficiency virus [HIV]) and Y721 (simian immunodeficiency virus
[SIV]) in the envelope glycoprotein (Env) of the primate lentiviruses
are crucial for the association of Env with clathrin-associated
adapter complex AP-2. The same tyrosine-based endocytosis
motifs in the cytosolic domains (EnvCD) of transmembrane gp41 of HIV
type 1 (HIV-1) and SIV, respectively, were also shown to
modulate the interaction with TGN- and endosome-based
clathrin-associated complex AP-1. Our findings suggested
that EnvCD binding to AP-1, unlike the association of EnvCD with AP-2,
is dependent largely on residues other than Y712 and Y721.
Here, we tested if motifs downstream of Y712 affect HIV-1
EnvCD-AP-1 binding and Env trafficking. Mutational analysis
revealed that the C-terminal leucine-based motif in Env was
crucial for the recruitment of AP-1 in vitro and in Env-expressing cells. In addition to affecting Env-AP-1 association, mutations at the
C terminus of Env also altered the subcellular localization of
Env, suggesting that proper post-Golgi routing of Env depends on
its recruitment of AP-1. Finally, the C-terminal dileucine was shown to assist the membrane-proximal Y712 motif in restricting the
cell surface expression of Env.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.6.2982-2992.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
The Highly Conserved C-Terminal Dileucine Motif in
the Cytosolic Domain of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Is Critical for Its Association with the AP-1
Clathrin Adapter

*
Corresponding author. Mailing address for Richard
Benarous: INSERM Unit 529, Interactions Moléculaires
Hôte-Pathogène, Institut Cochin de Génétique
Moléculaire, 24 Rue du Fg. St-Jaques, 75014 Paris, France. Phone:
33 1 44 41 25 65. Fax: 33 1 44 41 23 99. E-mail:
benarous{at}icgm.cochin.inserm.fr. Mailing address for
Markus Thali: University of Vermont, Department of Microbiology and Molecular Genetics, 320 Stafford Hall, Burlington, VT 05405. Phone: (802) 656-1056. Fax: (802) 656-8749. E-mail:
markus.thali{at}uvm.edu.
Present address: University of Pennsylvania, Department of
Hematology-Oncology, Philadelphia, PA 19104.
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