Developing new strategies to limit TRIM63/MuRF-1-mediated muscle protein loss - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2020

Developing new strategies to limit TRIM63/MuRF-1-mediated muscle protein loss

Dulce Peris-Moreno
Cécile Polge

Résumé

Skeletal muscle atrophy is defined as the decrease in muscle mass and muscle strength owing to injury, ageing, starvation, disuse or disease. Such muscle loss occurs upon protein homeostasis imbalance due to decreased protein synthesis and/or increased proteolysis, the latter being preponderant in most catabolic situations. Both the ubiquitin-dependent proteasome system (UPS) and the autophagy proteolytic pathways are activated during catabolic situations. In the specific case of the UPS, the muscle-specific E3-ligases, MuRF-1/TRIM63 is consistently upregulated under muscle atrophy and targets the proteins constituting the myofibrillar contractile system for subsequent degradation. In our case, due to the large overall protein content (80%) that the contractile apparatus represents for cells, it is important to study MuRF1 mechanism(s) of action and regulation. We study the modulation of MuRF1 activity by its companion ubiquitin-conjugating E2 enzymes. Indeed, MuRF1 binds to the substrates but the catalytic activity is brought by several E2 enzymes, each MuRF1-E2 couple having potentially different roles in muscle cells. In vitro methodologies (Surface Plasmon Resonance and MicroScale Thermophoresis) will reveal the MuRF1-E2-substrate interactions whereas in cellulo assays (gene overexpression and silencing) -in C2C12 muscle cells- will provide information about the impact of the MuRF-1-interacting E2s on skeletal muscle myofibers. Additionally, immunohistochemistry approaches in both C2C12 cells and mouse muscle tissue (tibialis anterior) will decipher the location of the different MuRF-1-interacting E2s. This will allow us to corroborate spatially the interactions observed in vitro.
Fichier principal
Vignette du fichier
POSTER JED-FINAL VERSION.pdf (9.16 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-04176196 , version 1 (02-08-2023)

Identifiants

  • HAL Id : hal-04176196 , version 1

Citer

Dulce Peris-Moreno, Daniel Taillandier, Cécile Polge. Developing new strategies to limit TRIM63/MuRF-1-mediated muscle protein loss. Journées scientifiques de l'École Doctorale (JEDs )des Sciences de la Vie, de la Santé, de l’Agronomie, et de l’Environnement (SVSAE), Oct 2020, Clermont-Ferrand, France. ⟨hal-04176196⟩
20 Consultations
2 Téléchargements

Partager

Gmail Facebook X LinkedIn More