Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse

Lasserre, Rémi; Charrin, Stéphanie; Cuche, Céline; Danckært, Anne; Thoulouze, María-Isabel; Chaumont, Fabrice de; Duong, Tarn; Perrault, Nathalie; Varin‐Blank, Nadine; Olivo‐Marin, Jean‐Christophe; Etienne-Manneville, Sandrine; Arpin, Monique; Bartolo, Vincenzo Di; Alcover, Andrés

doi:10.1038/emboj.2010.127

Cited by 113 publications

(176 citation statements)

References 53 publications

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“…This anchoring prevents IL-7R diffusion and stabilizes the recruitment of other receptors, such as integrin (10,26). Tubulin anchors to actin microfilaments, potentially through ezrin at its minusend (27), and polymerizes to form a microtubule that grows by its plus-end (28,29), crosses the cytoplasm, and reaches the nucleus less than 2 min after the addition of IL-7 (Figs. 3g and 7c).…”

Section: Sted Microscopy Analysis Of Il-7-induced Membrane Microdomaimentioning

confidence: 99%

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

Tamarit

Bugault

Pillet

et al. 2013

Journal of Biological Chemistry

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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.

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Section: Sted Microscopy Analysis Of Il-7-induced Membrane Microdomaimentioning

confidence: 99%

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

Tamarit

Bugault

Pillet

et al. 2013

Journal of Biological Chemistry

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“…Finally, other factors may also contribute to the interaction between actin and MTs to coordinate force generation (e.g., perturbation of ezrin-disrupted immune synapse shape) potentially by affecting the link between cortical actin and the MT network (67).…”

Section: Discussionmentioning

confidence: 99%

Dynamic microtubules regulate cellular contractility during T-cell activation

Hui

Upadhyaya

2017

Proc. Natl. Acad. Sci. U.S.A.

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T-cell receptor (TCR) triggering and subsequent T-cell activation are essential for the adaptive immune response. Recently, multiple lines of evidence have shown that force transduction across the TCR complex is involved during TCR triggering, and that the T cell might use its force-generation machinery to probe the mechanical properties of the opposing antigen-presenting cell, giving rise to different signaling and physiological responses. Mechanistically, actin polymerization and turnover have been shown to be essential for force generation by T cells, but how these actin dynamics are regulated spatiotemporally remains poorly understood. Here, we report that traction forces generated by T cells are regulated by dynamic microtubules (MTs) at the interface. These MTs suppress Rho activation, nonmuscle myosin II bipolar filament assembly, and actin retrograde flow at the T-cell-substrate interface. Our results suggest a novel role of the MT cytoskeleton in regulating force generation during T-cell activation.T lymphocytes, central players in the adaptive immune response, are activated when T-cell receptors (TCRs) on their surface recognize cognate peptide-major histocompatibility complex (pMHC) expressed on the surface of antigen-presenting cells (APCs). A burst of actin polymerization is triggered upon TCR stimulation (1), leading to an enhancement of the cell/APC contact area as the T cell spreads over the surface of the APC (2) and the formation of a macromolecular protein assembly known as the immunological synapse (IS) (3, 4). Accompanying IS formation, T cells also undergo a rapid polarization of the microtubule (MT) cytoskeleton, within 1-2 min after initial contact, that facilitates directional secretion of cytokines and cytolytic factors toward the APC (5-7). Therefore, the contact zone between T cells and APCs is a site at which the MT and actin cytoskeletons could potentially interact to regulate signaling.Recent studies have established that T cells generate significant traction stresses at the cell-cell interface, albeit relatively weak compared with adherent cells (8-11). These forces, which peak 5-10 min after stimulation, facilitate T-cell activation, in part, by inducing conformational changes in the TCR-CD3 complex (12-15). Although actin polymerization/depolymerization dynamics are essential for T cells to maintain dynamic traction stresses and to drive calcium influx and integrin affinity maturation (9, 16, 17), the regulatory pathways that control these cytoskeletal forces are not completely understood. In particular, whether and how the polarized MT cytoskeleton interacts with the actin cytoskeleton and regulates force generation at the T-cell-APC contact remain open questions.MTs in the cell exist in two populations: dynamic/tyrosinated MTs and stable MTs that have undergone posttranslational modifications, including detyrosination and acetylation (18). Previous studies of T-cell activation have elucidated that microtubuleorganizing center (MTOC) translocation is associated with the formati...

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“…105 Moreover, ERM proteins also play a role in cAMP-mediated T-cell repression by regulating PKA signaling. 106,107 In addition to Rho, PKCa and PKCh, recent studies have identified several GCK family members including MST1, MST4, NCK-interacting kinase (NIK) and lymphocyte-oriented kinase (LOK) as upstream kinases that can directly phosphorylate ERM.…”

Section: Gcks In Immune Regulationmentioning

confidence: 99%