MOB1 regulates thymocyte egress and T-cell survival in mice in a YAP1-independent manner

Wakako Kato, Miki Nishio, Yoko To, Hideru Togashi, Tak Wah Mak, Hidetoshi Takada, Shouichi Ohga, Tomohiko Maehama, Akira Suzuki

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Abstract

Mammalian STE20-like protein kinase 1/2 (MST1/2) and nuclear Dbf2-related kinase 1/2 (NDR1/2) are core components of Hippo signaling that are also known to be important regulators of lymphocyte trafficking. However, little is understood about the roles of other Hippo pathway molecules in these cells. Here, we present the first analysis of the function of Mps one binder kinase activator-1 (MOB1) in T lymphocytes in vivo. T-cell-specific double knockout (DKO) of MOB1A/B in mice [tMob1 DKO mice] reduces the number of naïve T cells in both the circulation and secondary lymphoid organs, but leads to an accumulation of CD4+CD8 and CD4CD8+ single-positive (SP) cells in the thymus. In vitro, naïve MOB1A/B-deficient T cells show increased apoptosis and display impaired trafficking capacity in response to the chemokine CCL19. These defects are linked to suppression of the activation of MST and NDR kinases, but are independent of the downstream transcriptional co-activator Yes-associated protein 1 (YAP1). Thus, MOB1 proteins play an important role in thymic egress and T-cell survival that is mediated by a pathway other than conventional Hippo-YAP1 signaling.

Original languageEnglish
Pages (from-to)485-495
Number of pages11
JournalGenes to Cells
Volume24
Issue number7
DOIs
Publication statusPublished - Jul 2019

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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    Kato, W., Nishio, M., To, Y., Togashi, H., Mak, T. W., Takada, H., Ohga, S., Maehama, T., & Suzuki, A. (2019). MOB1 regulates thymocyte egress and T-cell survival in mice in a YAP1-independent manner. Genes to Cells, 24(7), 485-495. https://doi.org/10.1111/gtc.12704