The kinases NDR1/2 act downstream of the Hippo homolog MST1 to mediate both egress of thymocytes from the thymus and lymphocyte motility.

Abstract

The serine and threonine kinase MST1 is the mammalian homolog of Hippo. MST1 is a critical mediator of the migration, adhesion, and survival of T cells; however, these functions of MST1 are independent of signaling by its typical effectors, the kinase LATS and the transcriptional coactivator YAP. The kinase NDR1, a member of the same family of kinases as LATS, functions as a tumor suppressor by preventing T cell lymphomagenesis, which suggests that it may play a role in T cell homeostasis. We generated and characterized mice with a T cell-specific double knockout of Ndr1 and Ndr2 (Ndr DKO). Compared with control mice, Ndr DKO mice exhibited a substantial reduction in the number of naïve T cells in their secondary lymphoid organs. Mature single-positive thymocytes accumulated in the thymus in Ndr DKO mice. We also found that NDRs acted downstream of MST1 to mediate the egress of mature thymocytes from the thymus, as well as the interstitial migration of naïve T cells within popliteal lymph nodes. Together, our findings indicate that the kinases NDR1 and NDR2 function as downstream effectors of MST1 to mediate thymocyte egress and T cell migration.

• Authors: Fengyuan Tang, Jason Gill, Xenia Ficht, Thomas Barthlott, Hauke Cornils, Debora Schmitz-Rohmer, Debby Hynx, Dawang Zhou, Lei Zhang, Gongda Xue, Michal Grzmil, Zhongzhou Yang, Alexander Hergovich, Georg A Hollaender, Jens V Stein, Brian A Hemmings, Patrick Matthias
• Journal: Science signaling (Sci Signal) Vol. 8 Issue 397 Pg. ra100 (Oct 06 2015) ISSN: 1937-9145 [Electronic] United States
• PMID: 26443704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Association for the Advancement of Science.

Chemical References

• Actins
• Stk4 protein, mouse
• NDR1 protein kinase, mouse
• NDR2 protein kinase, mouse
• Protein Serine-Threonine Kinases
• rho GTP-Binding Proteins

Topics

• Actins (physiology)
• Animals
• Apoptosis
• Cell Movement
• Chemotaxis
• Cytoskeleton (ultrastructure)
• Lymphocyte Count
• Lymphocytes (cytology)
• Lymphoid Tissue (pathology)
• Lymphopenia (enzymology, pathology)
• Mice
• Mice, Knockout
• Protein Serine-Threonine Kinases (deficiency, genetics, physiology)
• T-Lymphocyte Subsets (cytology)
• Thymocytes (cytology)
• Thymus Gland (pathology)
• Transendothelial and Transepithelial Migration (physiology)
• rho GTP-Binding Proteins (physiology)