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Sci Adv. 2017 Jun 21;3(6):e1603032. doi: 10.1126/sciadv.1603032. eCollection 2017 Jun.

Cytoskeletal actin dynamics shape a ramifying actin network underpinning immunological synapse formation.

Author information

1
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK.
2
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
3
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
4
Center for Biomembrane Physics (MEMPHYS), University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
5
Institut Curie, 26 rue d'Ulm, 75248 Paris cedex 05, France.
6
Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
7
Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
8
Wolfson Imaging Centre, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK.
9
Central Laser Facility, Rutherford Appleton Laboratory, Research Complex at Harwell, Science and Technology Facilities Council, Harwell-Oxford Campus, Didcot OX11 0FA, UK.
10
Department of Physics, King's College London, London WC2R 2LS, UK.
11
Vertex Pharmaceuticals, 11010 Torreyana Road, San Diego, CA 92121, USA.

Abstract

T cell activation and especially trafficking of T cell receptor microclusters during immunological synapse formation are widely thought to rely on cytoskeletal remodeling. However, important details on the involvement of actin in the latter transport processes are missing. Using a suite of advanced optical microscopes to analyze resting and activated T cells, we show that, following contact formation with activating surfaces, these cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse. This network shows all the characteristics of an inward-growing transportation network and its dynamics correlating with T cell receptor rearrangements. This actin reorganization is accompanied by an increase in the nanoscale actin meshwork size and the dynamic adjustment of the turnover times and filament lengths of two differently sized filamentous actin populations, wherein formin-mediated long actin filaments support a very flat and stiff contact at the immunological synapse interface. The initiation of immunological synapse formation, as highlighted by calcium release, requires markedly little contact with activating surfaces and no cytoskeletal rearrangements. Our work suggests that incipient signaling in T cells initiates global cytoskeletal rearrangements across the whole cell, including a stiffening process for possibly mechanically supporting contact formation at the immunological synapse interface as well as a central ramified transportation network apparently directed at the consolidation of the contact and the delivery of effector functions.

PMID:
28691087
PMCID:
PMC5479650
DOI:
10.1126/sciadv.1603032
[Indexed for MEDLINE]
Free PMC Article

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