|
| Status |
Public on Mar 27, 2023 |
| Title |
4E-BP1-dependent translation in nociceptors controls mechanical hypersensitivity via TRIM32/type I interferon signaling |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Activation of the mechanistic target of rapamycin complex 1 (mTORC1) contributes to the development of chronic pain. However, the specific mechanisms by which mTORC1 causes hypersensitivity remain elusive. The eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) is a key mTORC1 downstream effector that represses translation initiation. Here we show that nociceptor-specific deletion of 4E-BP1, mimicking activation of mTORC1-dependent translation, is sufficient to cause mechanical hypersensitivity.
|
| |
|
| Overall design |
Using the translating ribosome affinity purification in nociceptors lacking 4E-BP1, we identified a pronounced translational upregulation of TRIM32, an E3 ubiquitin ligase that promotes interferon signalling. Downregulation of TRIM32 in nociceptors or blocking type I interferon signaling reversed the mechanical hypersensitivity in mice lacking 4E-BP1. Furthermore, nociceptor-specific ablation of TRIM32 alleviated mechanical hypersensitivity caused by tissue inflammation. These results show that mTORC1 in nociceptors promotes hypersensitivity via 4E-BP1-dependent upregulation of TRIM32/interferon signaling and identify TRIM32 as a new therapeutic target in inflammatory pain.
|
| |
|
| Contributor(s) |
Khoutorsky A |
| Citation(s) |
37922363 |
| |
| Submission date |
Mar 22, 2023 |
| Last update date |
Nov 16, 2023 |
| Contact name |
Arkady Khoutorsky |
| E-mail(s) |
arkady.khoutorsky@mcgill.ca
|
| Organization name |
McGill University
|
| Department |
Department of Anesthesia and Faculty of Dentistry
|
| Lab |
Khoutorsky
|
| Street address |
McIntyre Medical Building, Room 1208
|
| City |
Montreal |
| ZIP/Postal code |
H3G 1Y6 |
| Country |
Canada |
| |
|
| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA947609 |
Less...
More...