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

PloS One
Ryunosuke MuroHarumi Suzuki

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 w...Continue Reading

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Citations

May 29, 2015·The Journal of Investigative Dermatology·Hong ChengYumin Xia
Apr 4, 2017·Acta Biochimica Et Biophysica Sinica·Dongguang GuoYugu Li
Oct 3, 2018·Biomedical Reports·Yoonjae ShinJong-Soo Chang
May 18, 2016·Biological Chemistry·Bhavin Shah, Andreas W Püschel
Jan 9, 2019·Ecology and Evolution·Anne DuplouyMarjo Saastamoinen
Jun 10, 2020·European Journal of Human Genetics : EJHG·Luca FerrariPaola Riva
Nov 16, 2021·Frontiers in Immunology·Suguru SaitoDerick Okwan-Duodu

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Methods Mentioned

BETA
nucleotide exchange
PCR
Assay
ELISA
flow cytometry
pull-down
FACS
GTPase

Software Mentioned

GraphPad Prism

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