title: The Ras GTPase-activating protein Rasal3 supports survival of naive T cells.
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.
authors: 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.
authors: Ryunosuke
authors: R
authors: Muro
authors: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Ichikawa-shi, Chiba, Japan.
authors: Takeshi
authors: T
authors: Nitta
authors: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Ichikawa-shi, Chiba, Japan.
authors: Toshiyuki
authors: T
authors: Okada
authors: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Ichikawa-shi, Chiba, Japan.
authors: Hitoshi
authors: H
authors: Ideta
authors: Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors: Takeshi
authors: T
authors: Tsubata
authors: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Ichikawa-shi, Chiba, Japan.
authors: Harumi
authors: H
authors: Suzuki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; C000599901:RASAL3 protein, mouse; D011948:Receptors, Antigen, T-Cell; D020703:ras GTPase-Activating Proteins