The MTM1-UBQLN2-HSP complex mediates degradation of misfolded intermediate filaments in skeletal muscle.
Fiche publication
Date publication
février 2018
Journal
Nature cell biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SUMARA Izabela, Mme MESSADDEQ Nadia
Tous les auteurs :
Gavriilidis C, Laredj L, Solinhac R, Messaddeq N, Viaud J, Laporte J, Sumara I, Hnia K
Lien Pubmed
Résumé
The ubiquitin proteasome system and autophagy are major protein turnover mechanisms in muscle cells, which ensure stemness and muscle fibre maintenance. Muscle cells contain a high proportion of cytoskeletal proteins, which are prone to misfolding and aggregation; pathological processes that are observed in several neuromuscular diseases called proteinopathies. Despite advances in deciphering the mechanisms underlying misfolding and aggregation, little is known about how muscle cells manage cytoskeletal degradation. Here, we describe a process by which muscle cells degrade the misfolded intermediate filament proteins desmin and vimentin by the proteasome. This relies on the MTM1-UBQLN2 complex to recognize and guide these misfolded proteins to the proteasome and occurs prior to aggregate formation. Thus, our data highlight a safeguarding function of the MTM1-UBQLN2 complex that ensures cytoskeletal integrity to avoid proteotoxic aggregate formation.
Référence
Nat. Cell Biol.. 2018 Feb;20(2):198-210