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| Status |
Public on Jul 29, 2024 |
| Title |
The nutrient sensor CRTC and Sarcalumenin/Thinman represent a new pathway in cardiac hypertrophy |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
CREB-Regulated Transcription Co-activator (CRTC) regulates metabolism in liver where activation by calcineurin regulates gluconeogenic genes. CaN also has roles in pathological cardiac hypertrophy, however cardiac roles for CRTC have not been identified. In Drosophila, CRTC null mutants exhibit severe cardiac restriction, myofibrillar disorganization, cardiac fibrosis, and tachycardia. Cardiac-specific knockdown (KD) of CRTC mimicked the heart defects of CRTC mutants and cardiac-overexpression (OE) of CRTC or calcineurin caused hypertrophy that was reduced in CRTC mutants, suggesting CRTC mediates calcineurin’s effects. RNAseq of CRTC KD or OE hearts revealed contra-regulated genes involved in glucose, fatty acid, and amino acid metabolism. Genes with conserved CREB binding sites included the fly ortholog of Sarcalumenin, a Ca2+-binding protein. Cardiac KD of this gene recapitulated CRTC KD restriction and fibrotic phenotypes. KD in zebrafish also caused restriction, indicating a conserved role in cardiomyocyte maintenance, and suggesting CaN-CRTC-Sarcalumenin signaling represents a novel pathway underlying cardiac hypertrophy.
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| Overall design |
We aimed at understanding the cardiac role of the CRTC co-factor by comparing gene expression in different experimental conditions.
For pan-tissue effects we prepared total RNA from wildtype and Crtc knock-out flies, while for heart-specific effects we used the heart-specific driver tinCdelta4-Gal4 to drive Crtc-RNAi and Crtc-overexpression (OE).
We used 6 samples for each genotype and performed differential gene expression analysis for the corresponding pairs.
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| Contributor(s) |
Dondi C, Walls S, Gupta A, Vogler G, Ocorr K |
| Citation(s) |
39093699 |
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| Submission date |
Jul 04, 2024 |
| Last update date |
Oct 28, 2024 |
| Contact name |
Georg Vogler |
| E-mail(s) |
[email protected]
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| Organization name |
Sanford Burnham Prebys Medical Discovery Institute
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| Street address |
10901 N Torrey Pines Road
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| City |
La Jolla |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL19132 |
Illumina NextSeq 500 (Drosophila melanogaster) |
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| Samples (26)
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| Relations |
| BioProject |
PRJNA1131800 |
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