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Computational spatiotemporal analysis identifies WAVE2 and cofilin as joint regulators of costimulation-mediated T cell actin dynamics

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Science Signaling  19 Apr 2016:
Vol. 9, Issue 424, pp. rs3
DOI: 10.1126/scisignal.aad4149

Imaging T cell actin dynamics

T cells must receive signals through the T cell receptor (TCR) and the costimulatory receptor CD28 to become fully activated. Critical to this process is the reorganization of plasma membrane actin at the immunological synapse, the interface between a T cell and an antigen-presenting cell. Roybal et al. imaged actin and fluorescently tagged actin regulatory proteins in T cells activated through the TCR in the absence or presence of CD28 signaling. Computational image processing to normalize differences in cell shape enabled tracking of the fluorescent proteins. The regulatory proteins WAVE2 and cofilin were efficiently recruited to the immunological synapse only when both TCR and CD28 signaled. Constitutive activation of either protein in TCR-stimulated T cells enabled normal actin reorganization even when CD28 signaling was blocked. This combination of imaging and computational analysis could be applied to other systems to determine the spatiotemporal dynamics of signaling molecules.

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