First Author | Tello-Lafoz M | Year | 2017 |
Journal | Sci Rep | Volume | 7 |
Issue | 1 | Pages | 16361 |
PubMed ID | 29180720 | Mgi Jnum | J:255770 |
Mgi Id | MGI:6110196 | Doi | 10.1038/s41598-017-16370-w |
Citation | Tello-Lafoz M, et al. (2017) SNX27 links DGKzeta to the control of transcriptional and metabolic programs in T lymphocytes. Sci Rep 7(1):16361 |
abstractText | 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 zeta (DGKzeta). SNX27 silencing in human T cells enhanced T cell receptor (TCR)-stimulated activator protein 1 (AP-1)- and nuclear factor kappaB (NF-kappaB)-mediated transcription. Transcription did not increase upon DGKzeta silencing, suggesting that DGKzeta 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. |