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PLoS One. 2015 Mar 20;10(3):e0119898. doi: 10.1371/journal.pone.0119898. eCollection 2015.

The Ras GTPase-activating protein Rasal3 supports survival of naive T cells.

Author information

1
Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Ichikawa-shi, Chiba, Japan; Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
2
Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Ichikawa-shi, Chiba, Japan.
3
Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

Abstract

The Ras-mitogen-activated protein kinase (MAPK) pathway is crucial for T cell receptor (TCR) signaling in the development and function of T cells. The significance of various modulators of the Ras-MAPK pathway in T cells, however, remains to be fully understood. Ras-activating protein-like 3 (Rasal3) is an uncharacterized member of the SynGAP family that contains a conserved Ras GTPase-activating protein (GAP) domain, and is predominantly expressed in the T cell lineage. In the current study, we investigated the function and physiological roles of Rasal3. Our results showed that Rasal3 possesses RasGAP activity, but not Rap1GAP activity, and represses TCR-stimulated ERK phosphorylation in a T cell line. In systemic Rasal3-deficient mice, T cell development in the thymus including positive selection, negative selection, and β-selection was unaffected. However, the number of naive, but not effector memory CD4 and CD8 T cell in the periphery was significantly reduced in Rasal3-deficient mice, and associated with a marked increase in apoptosis of these cells. Indeed, survival of Rasal3 deficient naive CD4 T cells in vivo by adoptive transfer was significantly impaired, whereas IL-7-dependent survival of naive CD4 T cells in vitro was unaltered. Collectively, Rasal3 is required for in vivo survival of peripheral naive T cells, contributing to the maintenance of optimal T cell numbers.

PMID:
25793935
PMCID:
PMC4368693
DOI:
10.1371/journal.pone.0119898
[Indexed for MEDLINE]
Free PMC Article

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