Membrane Microdomains and Cytoskeleton Organization Shape and Regulate the IL-7 Receptor Signalosome in Human CD4 T-cells

Abstract

Background: Interleukin-7 is the master regulator of T-cell proliferation. Results: IL-7 drives its receptor in a membrane microdomain that regulates phosphorylation of associated tyrosine kinases JAK1 and JAK3, anchors IL-7 receptor to cytoskeleton and regulates STAT5 phosphorylation and nuclear translocation. Conclusion: Membrane microdomains and cytoskeleton scaffold IL-7R-signalosomes and assist signaling protein transport. Significance: Transient membrane and cytoskeleton organization shapes IL-7-signaling mechanisms in CD4 T-cells.

Distinct Spatial Relationship of the Interleukin‐9 Receptor with Interleukin‐2 Receptor and Major Histocompatibility Complex Glycoproteins in Human T Lymphoma Cells

“…both types of IL-9Rα domains may be present on the same cell. It is plausible to assume that – similar to other members of the γ c receptor family – distribution (and/or redistribution) of IL-9 receptor chains between different membrane domains has a crucial role in regulating IL-9 evoked responses [41–43] . However, further experiments are required to elucidate the details and the factors regulating distribution of IL-9R between these distinct membrane areas.…”

Essential role of endocytosis for Interleukin-4 receptor mediated JAK/STAT signalling

“…Indeed, different processes may be used to subcellularly concentrate the various receptors, including clustering into lipid rafts or membrane associated signalosomes as reported for the IL-7R Tamarit et al, 2013) and the IL-2R systems. However, membrane (c) The relative rates of endocytosis and recycling lead to an increased receptor density at the cortical endosome limiting membrane, which locally shifts the equilibrium towards receptor heterodimerization.…”

Meeting Report – Visualizing signaling nanoplatforms at a higher spatiotemporal resolution

“…Thierry Rose and Bianca Tamarit showed that upon activation with IL-7, IL-7 receptors are compartmentalized into cholesterol-enriched membrane microdomains, from which the formation of an actin-microfilament meshwork is induced; here, anchored microtubules radially grow from the receptor domains towards the nuclear membrane. These radial microtubules allow phosphorylated STAT5 to glide across the cytoplasm and reach the nucleus within 2 minutes after IL-7 stimulation, with the microtubules disappearing at later time points after the signal has subsided (Tamarit et al, 2013).…”

“…Finally, two short presentations from Thierry Rose's group (Institute Pasteur, Paris, France) provided nice examples of combining the different super-resolution microscopy methods (STED, localization microscopy) with electron microscopy in a comprehensive approach to elucidate signal transduction during cytokineinduced cytoskeleton dynamics in human T cells via interleukin-7 (IL-7) receptors, and proposed a previously unappreciated role for microtubules in signal transduction (Tamarit et al, 2013). Thierry Rose and Bianca Tamarit showed that upon activation with IL-7, IL-7 receptors are compartmentalized into cholesterol-enriched membrane microdomains, from which the formation of an actin-microfilament meshwork is induced; here, anchored microtubules radially grow from the receptor domains towards the nuclear membrane.…”