The highly conserved C-terminal dileucine motif in the cytosolic domain ofthe human immunodeficiency virus type 1 envelope glycoprotein is critical for its association with the AP-1 clathrin adapter

Citation
S. Wyss et al., The highly conserved C-terminal dileucine motif in the cytosolic domain ofthe human immunodeficiency virus type 1 envelope glycoprotein is critical for its association with the AP-1 clathrin adapter, J VIROLOGY, 75(6), 2001, pp. 2982-2992
Citations number
55
Categorie Soggetti
Microbiology
Journal title
JOURNAL OF VIROLOGY
ISSN journal
0022538X → ACNP
Volume
75
Issue
6
Year of publication
2001
Pages
2982 - 2992
Database
ISI
SICI code
0022-538X(200103)75:6<2982:THCCDM>2.0.ZU;2-6
Abstract
Short amino acid sequences in the cytosolic domains of transmembrane protei ns are recognized by specialized adapter proteins which are part of coated vesicles utilized to transport membrane proteins between the trans-Golgi ne twork (TGN) and the plasma membrane (forward and backward). Previously, we and others reported that the membrane-proximal tyrosine residues Y712 (huma n immunodeficiency virus [HIV]) and Y721 (simian immunodeficiency virus [SI V]) in the envelope glycoprotein (Env) of the primate lentiviruses are cruc ial for the association of Env with clathrin-associated adapter complex AP- 2, The same tyrosine-based endocytosis motifs in the cytosolic domains (Env CD) of transmembrane gp41 of HIV type 1 (HIV-1) and SIV, respectively, were also shown to modulate the interaction with TGN- and endosome-based clathr in-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 resi dues 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 r evealed that the C-terminal leucine-based motif in Env was crucial for the recruitment of AP-T in vitro and in Env-expressing cells. In addition to af fecting Env-AP-1 association, mutations at the C terminus of Env also alter ed the subcellular localization of Env, suggesting that proper post-Golgi r outing of Env depends on its recruitment of AP-1. Finally, the C-terminal d ileucine was shown to assist the membrane-proximal Y712 motif in restrictin g the cell surface expression of Env.