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

Leonard L. Boer, Lesley Vanes, Serena Melgrati, Joshua Biggs O’May, Darryl Hayward, Paul C. Driscoll, Jason Day, Alexander Griffiths, Renata Magueta, Alexander Morrell, James I. MacRae, Robert Köchl and Victor L. J. Tybulewicz ()
Additional contact information
Leonard L. Boer: The Francis Crick Institute
Lesley Vanes: The Francis Crick Institute
Serena Melgrati: The Francis Crick Institute
Joshua Biggs O’May: The Francis Crick Institute
Darryl Hayward: The Francis Crick Institute
Paul C. Driscoll: The Francis Crick Institute
Jason Day: University of Cambridge
Alexander Griffiths: London Metallomics Facility, Research Management & Innovation Directorate, King’s College London
Renata Magueta: London Metallomics Facility, Research Management & Innovation Directorate, King’s College London
Alexander Morrell: London Metallomics Facility, Research Management & Innovation Directorate, King’s College London
James I. MacRae: The Francis Crick Institute
Robert Köchl: The Francis Crick Institute
Victor L. J. Tybulewicz: The Francis Crick Institute

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43423-8

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