WNK1 kinase balances T cell adhesion versus migration in vivo

The kinase WNK1 is part of a pathway that controls the uptake of ions into kidney cells. Tybulewicz and colleagues show that a related pathway involving WNK1 also operates in T cells, in which it negatively regulates adhesion and positively regulates migration. Adhesion and migration of T cells are...

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Published inNature immunology Vol. 17; no. 9; pp. 1075 - 1083
Main Authors Köchl, Robert, Thelen, Flavian, Vanes, Lesley, Brazão, Tiago F, Fountain, Kathryn, Xie, Jian, Huang, Chou-Long, Lyck, Ruth, Stein, Jens V, Tybulewicz, Victor L J
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.09.2016
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Abstract The kinase WNK1 is part of a pathway that controls the uptake of ions into kidney cells. Tybulewicz and colleagues show that a related pathway involving WNK1 also operates in T cells, in which it negatively regulates adhesion and positively regulates migration. Adhesion and migration of T cells are controlled by chemokines and by adhesion molecules, especially integrins, and have critical roles in the normal physiological function of T lymphocytes. Using an RNA-mediated interference screen, we identified the WNK1 kinase as a regulator of both integrin-mediated adhesion and T cell migration. We found that WNK1 is a negative regulator of integrin-mediated adhesion, whereas it acts as a positive regulator of migration via the kinases OXSR1 and STK39 and the ion co-transporter SLC12A2. WNK1-deficient T cells home less efficiently to lymphoid organs and migrate more slowly through them. Our results reveal that a pathway previously known only to regulate salt homeostasis in the kidney functions to balance T cell adhesion and migration.
AbstractList Adhesion and migration of T cells are controlled by chemokines and by adhesion molecules, especially integrins, and have critical roles in the normal physiological function of T lymphocytes. Using an RNA-mediated interference screen, we identified the WNK1 kinase as a regulator of both integrin-mediated adhesion and T cell migration. We found that WNK1 is a negative regulator of integrin-mediated adhesion, whereas it acts as a positive regulator of migration via the kinases OXSR1 and STK39 and the ion co-transporter SLC12A2. WNK1-deficient T cells home less efficiently to lymphoid organs and migrate more slowly through them. Our results reveal that a pathway previously known only to regulate salt homeostasis in the kidney functions to balance T cell adhesion and migration.
Adhesion and migration of T cells are controlled by chemokines and by adhesion molecules, especially integrins, and play critical roles in the normal physiological function of T lymphocytes. Using an RNA interference screen we have identified the WNK1 kinase as a regulator of both integrin-mediated adhesion and T cell migration. We demonstrate that WNK1 is a negative regulator of integrin-mediated adhesion, whereas it acts as a positive regulator of migration via OXSR1 and STK39 kinases and the SLC12A2 ion co-transporter. WNK1-deficient T cells home less efficiently to lymphoid organs, and migrate more slowly through them. Our results reveal that a pathway hitherto known only to regulate salt homeostasis in the kidney functions to balance T cell adhesion and migration.
The kinase WNK1 is part of a pathway that controls the uptake of ions into kidney cells. Tybulewicz and colleagues show that a related pathway involving WNK1 also operates in T cells, in which it negatively regulates adhesion and positively regulates migration. Adhesion and migration of T cells are controlled by chemokines and by adhesion molecules, especially integrins, and have critical roles in the normal physiological function of T lymphocytes. Using an RNA-mediated interference screen, we identified the WNK1 kinase as a regulator of both integrin-mediated adhesion and T cell migration. We found that WNK1 is a negative regulator of integrin-mediated adhesion, whereas it acts as a positive regulator of migration via the kinases OXSR1 and STK39 and the ion co-transporter SLC12A2. WNK1-deficient T cells home less efficiently to lymphoid organs and migrate more slowly through them. Our results reveal that a pathway previously known only to regulate salt homeostasis in the kidney functions to balance T cell adhesion and migration.
Audience Academic
Author Köchl, Robert
Fountain, Kathryn
Stein, Jens V
Lyck, Ruth
Xie, Jian
Thelen, Flavian
Vanes, Lesley
Huang, Chou-Long
Tybulewicz, Victor L J
Brazão, Tiago F
AuthorAffiliation 2 Theodor Kocher Institute, University of Bern, Bern, Switzerland
4 Department of Medicine, Imperial College, London, UK
1 The Francis Crick Institute, London, UK
3 University of Texas Southwestern Medical Center, Dallas, Texas, USA
AuthorAffiliation_xml – name: 3 University of Texas Southwestern Medical Center, Dallas, Texas, USA
– name: 2 Theodor Kocher Institute, University of Bern, Bern, Switzerland
– name: 1 The Francis Crick Institute, London, UK
– name: 4 Department of Medicine, Imperial College, London, UK
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  surname: Köchl
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  givenname: Lesley
  surname: Vanes
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/27400149$$D View this record in MEDLINE/PubMed
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Snippet The kinase WNK1 is part of a pathway that controls the uptake of ions into kidney cells. Tybulewicz and colleagues show that a related pathway involving WNK1...
Adhesion and migration of T cells are controlled by chemokines and by adhesion molecules, especially integrins, and have critical roles in the normal...
Adhesion and migration of T cells are controlled by chemokines and by adhesion molecules, especially integrins, and play critical roles in the normal...
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SubjectTerms 13
13/31
13/95
14
14/69
38/91
631/250/1619/554
631/250/516
631/80/84/1372
64
64/110
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Adhesion
Animals
Biomedicine
Cell adhesion
Cell Adhesion - genetics
Cell migration
Cell Movement - genetics
Cells, Cultured
Genetic aspects
Health aspects
Homeostasis
Immunology
Infectious Diseases
Ion Transport
Kidney - metabolism
Lymphocytes
Mice
Mice, Inbred C57BL
Mice, Knockout
Minor Histocompatibility Antigens - genetics
Minor Histocompatibility Antigens - metabolism
Phosphotransferases
Properties
Protein Serine-Threonine Kinases - genetics
Protein Serine-Threonine Kinases - metabolism
Receptors, Lymphocyte Homing - genetics
Receptors, Lymphocyte Homing - metabolism
RNA Interference
Solute Carrier Family 12, Member 2 - metabolism
T-Lymphocytes - physiology
WNK Lysine-Deficient Protein Kinase 1
Title WNK1 kinase balances T cell adhesion versus migration in vivo
URI https://link.springer.com/article/10.1038/ni.3495
https://www.ncbi.nlm.nih.gov/pubmed/27400149
https://www.proquest.com/docview/1812643468
https://www.proquest.com/docview/1812888839
https://search.proquest.com/docview/1815706139
https://pubmed.ncbi.nlm.nih.gov/PMC4994873
Volume 17
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