Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-017-16370-w
Title: SNX27 links DGK? to the control of transcriptional and metabolic programs in T lymphocytes
Authors: Tello-Lafoz, M
Rodríguez-Rodríguez, C
Kinna, G
Loo, L.S
Hong, W 
Collins, B.M
Teasdale, R.D
Mérida, I
Keywords: CD28 antigen
diacylglycerol kinase
diacylglycerol kinase zeta, human
interleukin 2
lymphocyte antigen receptor
protein kinase C alpha
SNX27 protein, human
Snx27 protein, mouse
sorting nexin
animal
biosynthesis
cell motion
energy metabolism
gene silencing
genetic transcription
genetics
human
immunology
Jurkat cell line
knockout mouse
lymphocyte activation
metabolism
signal transduction
T lymphocyte
Animals
CD28 Antigens
Cell Movement
Diacylglycerol Kinase
Energy Metabolism
Gene Silencing
Humans
Interleukin-2
Jurkat Cells
Lymphocyte Activation
Mice, Knockout
Protein Kinase C-alpha
Receptors, Antigen, T-Cell
Signal Transduction
Sorting Nexins
T-Lymphocytes
Transcription, Genetic
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Tello-Lafoz, M, Rodríguez-Rodríguez, C, Kinna, G, Loo, L.S, Hong, W, Collins, B.M, Teasdale, R.D, Mérida, I (2017). SNX27 links DGK? to the control of transcriptional and metabolic programs in T lymphocytes. Scientific Reports 7 (1) : 16361. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-017-16370-w
Rights: Attribution 4.0 International
Abstract: Sorting nexin 27 (SNX27) recycles PSD-95, Dlg1, ZO-1 (PDZ) domain-interacting membrane proteins and is essential to sustain adequate brain functions. Here we define a fundamental SNX27 function in T lymphocytes controlling antigen-induced transcriptional activation and metabolic reprogramming. SNX27 limits the activation of diacylglycerol (DAG)-based signals through its high affinity PDZ-interacting cargo DAG kinase ? (DGK?). SNX27 silencing in human T cells enhanced T cell receptor (TCR)-stimulated activator protein 1 (AP-1)-and nuclear factor ?B (NF-?B)-mediated transcription. Transcription did not increase upon DGK? silencing, suggesting that DGK? function is dependent on SNX27. The enhanced transcriptional activation in SNX27-silenced cells contrasted with defective activation of the mammalian target of rapamycin (mTOR) pathway. The analysis of Snx27 -/- mice supported a role for SNX27 in the control of T cell growth. This study broadens our understanding of SNX27 as an integrator of lipid-based signals with the control of transcription and metabolic pathways. © 2017 The Author(s).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/178555
ISSN: 2045-2322
DOI: 10.1038/s41598-017-16370-w
Rights: Attribution 4.0 International
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