Dissociation of ligand-induced internalization of CXCR-4 from its co-receptor activity for HIV-1 Env-mediated membrane fusion.
The C-terminal cytoplasmic tail of chemokine receptors is important for their internalization upon ligand binding. We generated several deletion mutants of the C-terminal cytoplasmic tail of CXCR-4, a co-receptor for T cell line tropic strains of human immunodeficiency virus type 1 (HIV-1), to know whether or not co-receptor internalization is associated with HIV-1 entry. Our data showed that the removal of C-terminal 15 amino acid residues of the cytoplasmic tail from CXCR-4 completely abolished its internalization, but did not affect the co-receptor activity at all. Co-receptor activity was fully retained even when all 45 amino acid residues in the C-terminal cytoplasmic tail had been deleted. These data indicated that no cytoplasmic tail nor internalization of CXCR-4 is required for its co-receptor activity for HIV-1 entry.
Hu
H
H
Department of Viral Infection, Institute of Medical Science, University of Tokyo, Japan.
Shioda
T
T
Hori
T
T
Moriya
C
C
Kato
A
A
Sakai
Y
Y
Matsushima
K
K
Uchiyama
T
T
Nagai
Y
Y
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D015686:Gene Products, env / Q000502:physiology*; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008024:Ligands; D008561:Membrane Fusion / Q000502:physiology*; D051379:Mice; D016133:Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D017384:Sequence Deletion
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D017931:DNA Primers; D015686:Gene Products, env; D008024:Ligands; D019718:Receptors, CXCR4; D011994:Recombinant Proteins