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© MPI f. Dynamik und Selbstorganisation
Publication : The Journal of biological chemistry

Interleukin-7 compartmentalizes its receptor signaling complex to initiate CD4 T lymphocyte response

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of biological chemistry - 18 Feb 2010

Rose T, Pillet AH, Lavergne V, Tamarit B, Lenormand P, Rousselle JC, Namane A, Thèze J

Link to Pubmed [PMID] – 20167604

J. Biol. Chem. 2010 May;285(20):14898-908

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.

http://www.ncbi.nlm.nih.gov/pubmed/20167604