Critical role of WNK1 in MYC-dependent early mouse thymocyte development

WNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4 T cells. is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in mouse thymocyte development. We find that WNK1 is required for...

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Published ineLife Vol. 9
Main Authors Köchl, Robert, Vanes, Lesley, Llorian Sopena, Miriam, Chakravarty, Probir, Hartweger, Harald, Fountain, Kathryn, White, Andrea, Cowan, Jennifer, Anderson, Graham, Tybulewicz, Victor Lj
Format Journal Article
LanguageEnglish
Published England eLife Science Publications, Ltd 14.10.2020
eLife Sciences Publications, Ltd
eLife Sciences Publications Ltd
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Summary:WNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4 T cells. is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in mouse thymocyte development. We find that WNK1 is required for the transition of double negative (DN) thymocytes through the β-selection checkpoint and subsequent proliferation and differentiation into double positive (DP) thymocytes. Furthermore, we show that WNK1 negatively regulates LFA1-mediated adhesion and positively regulates CXCL12-induced migration in DN thymocytes. Despite this, migration defects of WNK1-deficient thymocytes do not account for the developmental arrest. Instead, we show that in DN thymocytes WNK1 transduces pre-TCR signals via OXSR1 and STK39 kinases, and the SLC12A2 ion co-transporter that are required for post-transcriptional upregulation of MYC and subsequent proliferation and differentiation into DP thymocytes. Thus, a pathway regulating ion homeostasis is a critical regulator of thymocyte development.
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ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.56934