Editors' ChoiceImmunology

New connections: T cell actin dynamics

Sci. Signal.  19 Apr 2016:
Vol. 9, Issue 424, pp. ec95
DOI: 10.1126/scisignal.aaf8940

When T cells receive the appropriate signals through the T cell receptor (TCR) complex and the costimulatory receptor CD28, a complex rearrangement of the cytoskeleton occurs that enables the formation of the immunological synapse, a specialized structure that forms between the antigen-presenting cell and the T cell. In this week’s issue, Roybal et al. used sophisticated imaging of live cells and computational image analysis to visualize the dynamic rearrangements of actin and various regulatory proteins in T cells activated through the TCR in the absence or presence of CD28 signaling. The regulatory proteins WAVE2 and cofilin were efficiently recruited to the immunological synapse only when both TCR and CD28 signaled. Fried et al. used a different fluorescence imaging approach, triple-color FRET (fluorescence resonance energy transfer), to visualize not the movement of proteins with the cell, but the interactions between the actin-regulatory proteins WASp and WIP in live cells. The WASp-WIP interaction is required for T cell activation. The triple-color FRET analysis revealed how changes in the interaction between WASp and WIP resulted in WASp functioning as both an on and off switch. Although most studies' focus of T cell cytoskeletal dynamics is on the changes that occur at the immunological synapse, as González-Granado et al. showed, the nuclear cytoskeleton is also important for the immune response. In this study, live-cell imaging and immunofluorescence analysis revealed that nuclear lamin-A contributed to the polymerization of actin and, thus, immunological synapse formation. These studies highlight the insights that can be obtained about molecular dynamics from live-cell image analysis.

K. T. Roybal, T. E. Buck, X. Ruan, B. H. Cho, D. J. Clark, R. Ambler, H. M. Tunbridge, J. Zhang, P. Verkade, C. Wülfing, R. F. Murphy, Computational spatiotemporal analysis identifies WAVE2 and cofilin as joint regulators of costimulation-mediated T cell actin dynamics. Sci. Signal. 9, rs3 (2016). [Abstract]

S. Fried, B. Reicher, M. H. Pauker, S. Eliyahu, O. Matalon, E. Noy, J. Chill, M. Barda-Saad, Triple-color FRET analysis reveals conformational changes in the WIP-WASp actin-regulating complex. Sci. Signal. 7, ra60 (2014). [Abstract]

J. M. González-Granado, C. Silvestre-Roig, V. Rocha-Perugini, L. Trigueros-Motos, D. Cibrián, G. Morlino, M. Blanco-Berrocal, F. G. Osorio, J. M. P. Freije, C. López-Otín, F. Sánchez-Madrid, V. Andrés, Nuclear envelope Lamin-a couples actin dynamics with immunological synapse architecture and T cell activation. Sci. Signal. 7, ra37 (2014). [Abstract]

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