Fiche publication
Date publication
mars 2022
Journal
Proceedings of the National Academy of Sciences of the United States of America
Auteurs
Membres identifiés du Cancéropôle Est :
Mme MESSADDEQ Nadia
,
Mme KOEBEL Pascale
Tous les auteurs :
Lionello VM, Kretz C, Edelweiss E, Crucifix C, Gómez-Oca R, Messaddeq N, Buono S, Koebel P, Massana Muñoz X, Diedhiou N, Cowling BS, Bitoun M, Laporte J
Lien Pubmed
Résumé
The mechanoenzyme dynamin 2 (DNM2) is crucial for intracellular organization and trafficking. is mutated in dominant centronuclear myopathy (DNM2-CNM), a muscle disease characterized by defects in organelle positioning in myofibers. It remains unclear how the in vivo functions of DNM2 are regulated in muscle. Moreover, there is no therapy for DNM2-CNM to date. Here, we overexpressed human amphiphysin 2 (BIN1), a membrane remodeling protein mutated in other CNM forms, in and mice modeling mild and severe DNM2-CNM, through transgenesis or with adeno-associated virus (AAV). Increasing BIN1 improved muscle atrophy and main histopathological features of mice and rescued the perinatal lethality and survival of mice. In vitro experiments showed that BIN1 binds and recruits DNM2 to membrane tubules, and that the BIN1-DNM2 complex regulates tubules fission. Overall, BIN1 is a potential therapeutic target for dominant centronuclear myopathy linked to DNM2 mutations.
Mots clés
amphiphysin, congenital myopathy, dynamin, gene therapy, membrane remodeling
Référence
Proc Natl Acad Sci U S A. 2022 Mar 1;119(9):
