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T cell migration requires ion and water influx to regulate actin polymerization.

Published version
Peer-reviewed

Repository DOI


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Authors

Vanes, Lesley 
Melgrati, Serena 
Biggs O'May, Joshua 
Hayward, Darryl 

Abstract

Migration of T cells is essential for their ability to mount immune responses. Chemokine-induced T cell migration requires WNK1, a kinase that regulates ion influx into the cell. However, it is not known why ion entry is necessary for T cell movement. Here we show that signaling from the chemokine receptor CCR7 leads to activation of WNK1 and its downstream pathway at the leading edge of migrating CD4+ T cells, resulting in ion influx and water entry by osmosis. We propose that WNK1-induced water entry is required to swell the membrane at the leading edge, generating space into which actin filaments can polymerize, thereby facilitating forward movement of the cell. Given the broad expression of WNK1 pathway proteins, our study suggests that ion and water influx are likely to be essential for migration in many cell types, including leukocytes and metastatic tumor cells.

Description

Acknowledgements: We thank Erik Sahai and Michael Way for critical reading of this manuscript. We thank Rachel Edgar and John O’Neill for helpful discussions. We thank Miriam Llorian Sopena for help with analysis of RNA-seq data. We thank the Advanced Light Microscopy, Flow Cytometry and Biological Research Facilities of the Francis Crick Institute for microscopy, flow cytometry and for animal husbandry. We thank Chou-Long Huang, Dario Alessi and Sung-Sen Yang for mouse strains. We thank Rachel Toth for generation of plasmids, and the MRC Protein Phosphorylation Unit for antibodies. V.L.J.T. was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2080), the UK Medical Research Council (CC2080), and the Wellcome Trust (CC2080), and by a grant from UKRI Biotechnology and Biological Sciences Research Council (BB/V0088757/1). This work was partly supported by the Francis Crick Institute through provision of access to the MRC Biomedical NMR Centre. L.L.d.B. was funded by an Imperial College London President’s PhD Scholarship. For the purpose of Open Access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

Keywords

Actins, Polymerization, Cell Movement, Actin Cytoskeleton, Signal Transduction

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

14

Publisher

Springer Science and Business Media LLC
Sponsorship
Francis Crick Institute (Francis Crick Institute Limited) (CC2080)
Cancer Research UK (CRUK) (CC2080)
RCUK | Medical Research Council (MRC) (CC2080)
Wellcome Trust (Wellcome) (CC2080)