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| Status |
Public on Feb 20, 2009 |
| Title |
Activation of mTOR controls the loss of TCRζ in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
CD3-positive T cells were negatively isolated from 10 SLE patients and 9 healthy controls without SLE. All of the SLE samples and control samples were compared with one another to identify baseline differences in expression due to the disease. Next, T cell preparations from 4 of the control subjects were stimulated with either Nitric Oxide (NOC-18) 600 uM for 24hr or stimulated through CD3/CD28 for 24hr to determine which genes were responsive to these signaling mechanisms. Here, we show that activity of the mammalian target of rapamycin (mTOR), which is a sensor of the mitochondrial transmembrane potential, is increased in SLE T cells. Activation of mTOR was inducible by NO, a key trigger of MHP which in turn enhanced the expression of HRES-1/Rab4, a small GTPase that regulates recycling of surface receptors through early endosomes. Expression of HRES-1/Rab4 was increased in SLE T cells and, in accordance with its dominant impact on the endocytic recycling of CD4, it was inversely correlated with diminished CD4 expression. HRES-1/Rab4 over-expression was also inversely correlated with diminished TCRζ protein levels. Combined with follow up studies, these results suggest that activation of mTOR causes the loss of TCRζ in lupus T cells through HRES-1/Rab4-dependent lysosomal degradation.
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| Overall design |
10 replicate T cell samples from SLE (Lupus) patients
9 replicate T cell samples from healthy control (BC) subjects
4 replicate Nitric Oxide (NOC-18) stimulated T cell samples from 4 of the control subjects
4 replicate CD3/CD28 stimulated T cell samples from 4 of the control subjects
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| Contributor(s) |
Fernandez DR, Telarico T, Bonilla E, Li Q, Banerjee S, Middleton FA, Phillips PE, Crow MK, Oess S, Muller-Esterl W, Perl A |
| Citation(s) |
19201859 |
| Submission date |
Dec 09, 2008 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Frank A Middleton |
| E-mail(s) |
middletf@upstate.edu
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| Phone |
315-464-7721
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| Organization name |
SUNY Upstate Medical Univ
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| Department |
Neuroscience and Physiology
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| Street address |
505 Irving Avenue
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| City |
Syracuse |
| State/province |
NY |
| ZIP/Postal code |
13210 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (27)
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| Relations |
| BioProject |
PRJNA110359 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE13887_RAW.tar |
130.5 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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