Titre : | A centronuclear myopathy-dynamin2 mutation impairs autophagy in mice |
contenu dans : | |
Auteurs : | 4th International Congress of Myology, 4ème colloque international de Myologie (9-13 mai 2011; Lille (France)) ; Durieux AC ; Vassilopoulos S ; Laine J ; Fraysse B ; Prudhon B ; Freyssenet D ; Bonne G ; Guicheney P ; Bitoun M |
Type de document : | Article |
Année de publication : | 2011 |
Pages : | p. 59 |
Langues: | Anglais |
Mots-clés : | colloque |
Résumé : | Dynamin 2 (DNM2) is involved in endocytosis and intracellular membrane trafficking through its function in vesicle formation and release from distinct membrane compartments. Mutations in the DNM2 gene cause autosomal dominant centronuclear myopathy (CNM) and rare forms of Charcot-Marie-Tooth peripheral neuropathy. Recently, we constructed a knock-in mouse model expressing the most frequent human CNM mutation (KI-Dnm2R465W). Heterozygous mice developed a myopathy sharing similarities with human disease whereas homozygous mice died during the day of delivery. We investigated here the hypothesis of an impairment of the autophagic pathway as cause of neonatal lethality. Our results suggest that a defect of neonatal autophagy in liver may be the cause of the lethality. In vitro study performed in embryonic fibroblasts pointed out that homozygous DNM2 mutation leads to a decrease in the flux of autophagy associated with a defect in the autophagosome maturation. Our results highlight the crosstalk between endocytic and autophagic pathways and show a role of the DNM2-dependent intracellular membrane trafficking in autophagy which may be relevant in the DNM2-related diseases. |