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
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
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.