Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion.
Leukocyte trafficking at the endothelium requires both cellular adhesion molecules and chemotactic factors. Fractalkine, a novel transmembrane molecule with a CX3C-motif chemokine domain atop a mucin stalk, induces both adhesion and migration of leukocytes. Here we identify a seven-transmembrane high-affinity receptor for fractalkine and show that it mediates both the adhesive and migratory functions of fractalkine. The receptor, now termed CX3CR1, requires pertussis toxin-sensitive G protein signaling to induce migration but not to support adhesion, which also occurs without other adhesion molecules but requires the architecture of a chemokine domain atop the mucin stalk. Natural killer cells predominantly express CX3CR1 and respond to fractalkine in both migration and adhesion. Thus, fractalkine and CX3CR1 represent new types of leukocyte trafficking regulators, performing both adhesive and chemotactic functions.
Imai
T
T
Shionogi Institute for Medical Science, Settsu, Japan.
Hieshima
K
K
Haskell
C
C
Baba
M
M
Nagira
M
M
Nishimura
M
M
Kakizaki
M
M
Takagi
S
S
Nomiyama
H
H
Schall
T J
TJ
Yoshie
O
O
D015703:Antigens, CD / Q000032:analysis; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D018925:Chemokines / Q000378:metabolism*; D020523:Chemokines, CX3C; D004730:Endothelium, Vascular / Q000276:immunology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D007962:Leukocytes / Q000166:cytology*; D016131:Lymphocyte Subsets; D008565:Membrane Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D019707:Receptors, Chemokine / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins
D015703:Antigens, CD; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D018925:Chemokines; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D019204:GTP-Binding Proteins