ArticleThe Journal of biological chemistry2013
Membrane microdomains and cytoskeleton organization shape and regulate the IL-7 receptor signalosome in human CD4 T-cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Suppression of macrophage membrane cholesterol efflux by SLAMF7-induced IL-7 signaling improves immunotherapy efficacy in hepatocellular carcinoma.Hepatology international · 2026Article
- Wilforine attenuates inflammatory osteolysis by suppressing osteoclast fusion through JAK-STAT-stomatin immunoregulatory signaling.Frontiers in immunology · 2026Article
- Location, location, location: Protein kinase nanoclustering for optimised signalling output.eLife · 2024Review
- THEMIS is a substrate and allosteric activator of SHP1, playing dual roles during T cell development.Nature structural & molecular biology · 2024Article
- Proteomic analysis in primary T cells reveals IL-7 alters T cell receptor thresholding via CYTIP/cytohesin/LFA-1 localisation and activation.The Biochemical journal · 2022Article
- Cytokine receptor cluster size impacts its endocytosis and signaling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- DNA methylation of JAK3/STAT5/PPARγ regulated the changes of lipid levels induced by di (2-ethylhexyl) phthalate and high-fat diet in adolescent rats.Environmental science and pollution research international · 2020Article
- Introducing variability in targeting the microtubules: Review of current mechanisms and future directions in colchicine therapy.Pharmacology research & perspectives · 2020Review
- PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients.The Journal of clinical investigation · 2020Article
- The Tetraspanin CD53 Regulates Early B Cell Development by Promoting IL-7R Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Deleterious and Oncogenic Mutations in theCancers · 2019Review
- Lztfl1/BBS17 controls energy homeostasis by regulating the leptin signaling in the hypothalamic neurons.Journal of molecular cell biology · 2018Article
- Saracatinib impairs maintenance of human T-ALL by targeting the LCK tyrosine kinase in cells displaying high level of lipid rafts.Leukemia · 2018Article
- Visualizing the Actin and Microtubule Cytoskeletons at the B-cell Immune Synapse Using Stimulated Emission Depletion (STED) Microscopy.Journal of visualized experiments : JoVE · 2018Article
- MHC I Expression Regulates Co-clustering and Mobility of Interleukin-2 and -15 Receptors in T Cells.Biophysical journal · 2016Article
- Focusing super resolution on the cytoskeleton.F1000Research · 2016Review
- Article
- TCR and IL-7 Signaling Are Altered in the Absence of Functional GTPase of the Immune Associated Nucleotide Binding Protein 5 (GIMAP5).PloS one · 2016Article
- Distinct spatial relationship of the interleukin-9 receptor with interleukin-2 receptor and major histocompatibility complex glycoproteins in human T lymphoma cells.Chemphyschem : a European journal of chemical physics and physical chemistry · 2014Article
- Dynamics and interaction of interleukin-4 receptor subunits in living cells.Biophysical journal · 2014Article
Corrections and comments
- Correction · 2019-03-29Error in Image ·
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin (IL)-7 is the main homeostatic regulator of CD4 T-lymphocytes (helper) at both central and peripheral levels. Upon activation by IL-7, several signaling pathways, mainly JAK/STAT, PI3K/Akt and MAPK, induce the expression of genes involved in T-cell differentiation, activation, and proliferation. We have analyzed the early events of CD4 T-cell activation by IL-7. We have shown that IL-7 in the first few min induces the formation of cholesterol-enriched membrane microdomains that compartmentalize its activated receptor and initiate its anchoring to the cytoskeleton, supporting the formation of the signaling complex, the signalosome, on the IL-7 receptor cytoplasmic domains. Here we describe by stimulated emission depletion microscopy the key roles played by membrane microdomains and cytoskeleton transient organization in the IL-7-regulated JAK/STAT signaling pathway. We image phospho-STAT5 and cytoskeleton components along IL-7 activation kinetics using appropriate inhibitors. We show that lipid raft inhibitors delay and reduce IL-7-induced JAK1 and JAK3 phosphorylation. Drug-induced disassembly of the cytoskeleton inhibits phospho-STAT5 formation, transport, and translocation into the nucleus that controls the transcription of genes involved in T-cell activation and proliferation. We fit together the results of these quantitative analyses and propose the following mechanism. Activated IL-7 receptors embedded in membrane microdomains induce actin-microfilament meshwork formation, anchoring microtubules that grow radially from rafted receptors to the nuclear membrane. STAT5 phosphorylated by signalosomes are loaded on kinesins and glide along the microtubules across the cytoplasm to reach the nucleus 2 min after IL-7 stimulation. Radial microtubules disappear 15 min later, while transversal microtubules, independent of phospho-STAT5 transport, begin to bud from the microtubule organization center.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.