ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Gene targeting RhoA reveals its essential role in coordinating mitochondrial function and thymocyte development.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.Frontiers in immunology · 2026Review
- Advances in the pathogenesis and therapeutic strategies of angioimmunoblastic T-cell lymphoma.Clinical and experimental medicine · 2023Review
- Review
- Review
- RhoA and Cdc42 in T cells: Are they targetable for T cell-mediated inflammatory diseases?Precision clinical medicine · 2021Article
- Review
- The Metabolic Landscape of Thymic T Cell DevelopmentFrontiers in immunology · 2021Article
- Journey to the Center of the Cell: Cytoplasmic and Nuclear Actin in Immune Cell Functions.Frontiers in cell and developmental biology · 2021Review
- Review
- Review
- RhoA/Rho-kinases in asthma: from pathogenesis to therapeutic targets.Clinical & translational immunology · 2020Review
- Genomics of Peripheral T-Cell Lymphoma and Its Implications for Personalized Medicine.Frontiers in oncology · 2020Review
- Ablation of RhoA impairs Th17 cell differentiation and alleviates house dust mite-triggered allergic airway inflammation.Journal of leukocyte biology · 2019Article
- Review
- Stressed: The Unfolded Protein Response in T Cell Development, Activation, and Function.International journal of molecular sciences · 2019Review
- Activation of cyclin D1 affects mitochondrial mass following traumatic brain injury.Neurobiology of disease · 2018Article
- Pseudomonas aeruginosa ExoS Induces Intrinsic Apoptosis in Target Host Cells in a Manner That is Dependent on its GAP Domain Activity.Scientific reports · 2018Article
- Overexpression of Myosin Phosphatase Target Subunit 1 (MYPT1) Inhibits Tumor Progression and Metastasis of Gastric Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Review of the biologic and clinical significance of genetic mutations in angioimmunoblastic T-cell lymphoma.Cancer science · 2018Review
- Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Thymocyte development is regulated by complex signaling pathways. How these signaling cascades are coordinated remains elusive. RhoA of the Rho family small GTPases plays an important role in actin cytoskeleton organization, cell adhesion, migration, proliferation, and survival. Nonetheless, the physiological function of RhoA in thymocyte development is not clear. By characterizing a conditional gene targeting mouse model bearing T cell deletion of RhoA, we show that RhoA critically regulates thymocyte development by coordinating multiple developmental events. RhoA gene disruption caused a strong developmental block at the pre-TCR checkpoint and during positive selection. Ablation of RhoA led to reduced DNA synthesis in CD4(-)CD8(-), CD4(+)CD8(-), and CD4(-)CD8(+) thymocytes but not in CD4(+)CD8(+) thymocytes. Instead, RhoA-deficient CD4(+)CD8(+) thymocytes showed an impaired mitosis. Furthermore, we found that abrogation of RhoA led to an increased apoptosis in all thymocyte subpopulations. Importantly, we show that the increased apoptosis was resulted from reduced pre-TCR expression and increased production of reactive oxygen species (ROS), which may be because of an enhanced mitochondrial function, as manifested by increased oxidative phosphorylation, glycolysis, mitochondrial membrane potential, and mitochondrial biogenesis in RhoA-deficient thymocytes. Restoration of pre-TCR expression or treatment of RhoA-deficient mice with a ROS scavenger N-acetylcysteine partially restored thymocyte development. These results suggest that RhoA is required for thymocyte development and indicate, to our knowledge, for the first time that fine-tuning of ROS production by RhoA, through a delicate control of metabolic circuit, may contribute to thymopoiesis.
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