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2 Janelia Publications

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    03/19/19 | Cytoskeletal control of antigen-dependent T cell activation.
    Colin-York H, Javanmardi Y, Skamrahl M, Kumari S, Chang VT, Khuon S, Taylor A, Chew T, Betzig E, Moeendarbary E, Cerundolo V, Eggeling C, Fritzsche M
    Cell Reports. 2019 Mar 19;26(12):3369-3379.e5. doi: 10.1016/j.celrep.2019.02.074

    Cytoskeletal actin dynamics is essential for T cell activation. Here, we show evidence that the binding kinetics of the antigen engaging the T cell receptor influences the nanoscale actin organization and mechanics of the immune synapse. Using an engineered T cell system expressing a specific T cell receptor and stimulated by a range of antigens, we found that the peak force experienced by the T cell receptor during activation was independent of the unbinding kinetics of the stimulating antigen. Conversely, quantification of the actin retrograde flow velocity at the synapse revealed a striking dependence on the antigen unbinding kinetics. These findings suggest that the dynamics of the actin cytoskeleton actively adjusted to normalize the force experienced by the T cell receptor in an antigen-specific manner. Consequently, tuning actin dynamics in response to antigen kinetics may thus be a mechanism that allows T cells to adjust the lengthscale and timescale of T cell receptor signaling.

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    03/07/19 | Cytoskeletal actin patterns shape mast cell activation.
    Colin-York H, Li D, Korobchevskaya K, Chang VT, Betzig E, Eggeling C, Fritzsche M
    Communications Biology. 2019;2:93. doi: 10.1038/s42003-019-0322-9

    Activation of immune cells relies on a dynamic actin cytoskeleton. Despite detailed knowledge of molecular actin assembly, the exact processes governing actin organization during activation remain elusive. Using advanced microscopy, we here show that Rat Basophilic Leukemia (RBL) cells, a model mast cell line, employ an orchestrated series of reorganization events within the cortical actin network during activation. In response to IgE antigen-stimulation of FCε receptors (FCεR) at the RBL cell surface, we observed symmetry breaking of the F-actin network and subsequent rapid disassembly of the actin cortex. This was followed by a reassembly process that may be driven by the coordinated transformation of distinct nanoscale F-actin architectures, reminiscent of self-organizing actin patterns. Actin patterns co-localized with zones of Arp2/3 nucleation, while network reassembly was accompanied by myosin-II activity. Strikingly, cortical actin disassembly coincided with zones of granule secretion, suggesting that cytoskeletal actin patterns contribute to orchestrate RBL cell activation.

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