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

• Published in: Nature communications Vol. 14; no. 1; p. 7844
• Main Authors: de Boer, Leonard L., Vanes, Lesley, Melgrati, Serena, Biggs O’May, Joshua, Hayward, Darryl, Driscoll, Paul C., Day, Jason, Griffiths, Alexander, Magueta, Renata, Morrell, Alexander, MacRae, James I., Köchl, Robert, Tybulewicz, Victor L. J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.12.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/31; 13/95; 14; 14/63; 631/250/1619/554/1898; 631/250/2503; 631/250/98; 631/80/84; 64/60; Actin; Actin Cytoskeleton - metabolism; Actins - metabolism; CD4 antigen; Cell adhesion & migration; Cell migration; Cell Movement - physiology; Chemokine receptors; Chemokines; Filaments; Humanities and Social Sciences; Kinases; Leading edges; Lymphocytes; Lymphocytes T; Medicin och hälsovetenskap; Membranes; Metastases; multidisciplinary; Osmosis; Polymerization; Science; Science (multidisciplinary); Signal Transduction - physiology; Tumor cells
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43423-8

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. The ability of T cells to migrate is a central component of their functionality and is known to require WNK1 kinase that is linked to the influx of ions into the cell. Here the authors show that T cell migration requires WNK1 mediated ion and water influx to swell the membrane of the leading edge and support actin polymerisation and forward motility.