Interleukin-7 compartmentalizes its receptor signaling complex to initiate CD4 T lymphocyte response.
Interleukin (IL)-7 is a central cytokine that controls homeostasis of the CD4 T lymphocyte pool. Here we show on human primary cells that IL-7 binds to preassembled receptors made up of proprietary chain IL-7Ralpha and the common chain gammac shared with IL-2, -4, -9, -15, and -21 receptors. Upon IL-7 binding, both chains are driven in cholesterol- and sphingomyelin-rich rafts where associated signaling proteins Jak1, Jak3, STAT1, -3, and -5 are found to be phosphorylated. Meanwhile the IL-7.IL-7R complex interacts with the cytoskeleton that halts its diffusion as measured by single molecule fluorescence autocorrelated spectroscopy monitored by microimaging. Comparative immunoprecipitations of IL-7Ralpha signaling complex from non-stimulated and IL-7-stimulated cells confirmed recruitment of proteins such as STATs, but many others were also identified by mass spectrometry from two-dimensional gels. Among recruited proteins, two-thirds are involved in cytoskeleton and raft formation. Thus, early events leading to IL-7 signal transduction involve its receptor compartmentalization into membrane nanodomains and cytoskeleton recruitment.
Rose
Thierry
T
Institut Pasteur, Unité d'Immunogénétique Cellulaire, Département Infection et Epidémiologie, Département d'Immunologie, Genopole, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Electronic address: rose@pasteur.fr.
Pillet
Anne-Hélène
AH
Institut Pasteur, Unité d'Immunogénétique Cellulaire, Département Infection et Epidémiologie, Département d'Immunologie, Genopole, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Lavergne
Vincent
V
Institut Pasteur, Unité d'Immunogénétique Cellulaire, Département Infection et Epidémiologie, Département d'Immunologie, Genopole, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Tamarit
Blanche
B
Institut Pasteur, Unité d'Immunogénétique Cellulaire, Département Infection et Epidémiologie, Département d'Immunologie, Genopole, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Lenormand
Pascal
P
Plate-Forme Protéomique, Genopole, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Rousselle
Jean-Claude
JC
Plate-Forme Protéomique, Genopole, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Namane
Abdelkader
A
Plate-Forme Protéomique, Genopole, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Thèze
Jacques
J
Institut Pasteur, Unité d'Immunogénétique Cellulaire, Département Infection et Epidémiologie, Département d'Immunologie, Genopole, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002451:Cell Compartmentation; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D047468:Immunoprecipitation; D015851:Interleukin-7 / Q000378:metabolism*; D008213:Lymphocyte Activation; D013058:Mass Spectrometry; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence; D014461:Ultracentrifugation
D015851:Interleukin-7; D020395:Receptors, Interleukin-7