PMID- 29180720
OWN - NLM
STAT- MEDLINE
DCOM- 20190712
LR  - 20210616
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Nov 27
TI  - SNX27 links DGKzeta to the control of transcriptional and metabolic programs in T 
      lymphocytes.
PG  - 16361
LID - 10.1038/s41598-017-16370-w [doi]
LID - 16361
AB  - 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.
FAU - Tello-Lafoz, M
AU  - Tello-Lafoz M
AUID- ORCID: 0000-0001-8909-6800
AD  - Department of Immunology and Oncology, Centro Nacional de Biotecnologia 
      (CNB-CSIC), Darwin 3, Campus UAM Cantoblanco, 28079, Madrid, Spain.
FAU - Rodriguez-Rodriguez, C
AU  - Rodriguez-Rodriguez C
AD  - Department of Immunology and Oncology, Centro Nacional de Biotecnologia 
      (CNB-CSIC), Darwin 3, Campus UAM Cantoblanco, 28079, Madrid, Spain.
FAU - Kinna, G
AU  - Kinna G
AD  - Institute for Molecular Bioscience, The University of Queensland, St. Lucia, 
      Queensland, 4072, Australia.
FAU - Loo, L S
AU  - Loo LS
AD  - Institute of Molecular and Cell Biology A* STAR, Singapore, 138673, Singapore.
FAU - Hong, W
AU  - Hong W
AD  - Institute of Molecular and Cell Biology A* STAR, Singapore, 138673, Singapore.
FAU - Collins, B M
AU  - Collins BM
AD  - Institute for Molecular Bioscience, The University of Queensland, St. Lucia, 
      Queensland, 4072, Australia.
FAU - Teasdale, R D
AU  - Teasdale RD
AD  - Institute for Molecular Bioscience, The University of Queensland, St. Lucia, 
      Queensland, 4072, Australia.
AD  - School of Biomedical Sciences, The University of Queensland, St. Lucia, 
      Queensland, 4072, Australia.
FAU - Merida, I
AU  - Merida I
AD  - Department of Immunology and Oncology, Centro Nacional de Biotecnologia 
      (CNB-CSIC), Darwin 3, Campus UAM Cantoblanco, 28079, Madrid, Spain. 
      imerida@cnb.csic.es.
LA  - eng
PT  - Journal Article
DEP - 20171127
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (CD28 Antigens)
RN  - 0 (Interleukin-2)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (SNX27 protein, human)
RN  - 0 (Snx27 protein, mouse)
RN  - 0 (Sorting Nexins)
RN  - EC 2.7.1.107 (DGKZ protein, human)
RN  - EC 2.7.1.107 (Diacylglycerol Kinase)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
SB  - IM
MH  - Animals
MH  - CD28 Antigens/metabolism
MH  - Cell Movement/genetics/immunology
MH  - Diacylglycerol Kinase/*metabolism
MH  - *Energy Metabolism
MH  - Gene Silencing
MH  - Humans
MH  - Interleukin-2/biosynthesis
MH  - Jurkat Cells
MH  - Lymphocyte Activation
MH  - Mice, Knockout
MH  - Protein Kinase C-alpha/metabolism
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - Signal Transduction
MH  - Sorting Nexins/genetics/*metabolism
MH  - T-Lymphocytes/immunology/*metabolism
MH  - *Transcription, Genetic
PMC - PMC5703713
COIS- The authors declare that they have no competing interests.
EDAT- 2017/11/29 06:00
MHDA- 2019/07/13 06:00
PMCR- 2017/11/27
CRDT- 2017/11/29 06:00
PHST- 2017/07/20 00:00 [received]
PHST- 2017/11/10 00:00 [accepted]
PHST- 2017/11/29 06:00 [entrez]
PHST- 2017/11/29 06:00 [pubmed]
PHST- 2019/07/13 06:00 [medline]
PHST- 2017/11/27 00:00 [pmc-release]
AID - 10.1038/s41598-017-16370-w [pii]
AID - 16370 [pii]
AID - 10.1038/s41598-017-16370-w [doi]
PST - epublish
SO  - Sci Rep. 2017 Nov 27;7(1):16361. doi: 10.1038/s41598-017-16370-w.