| First Author | Durieux AC | Year | 2012 |
| Journal | Traffic | Volume | 13 |
| Issue | 6 | Pages | 869-79 |
| PubMed ID | 22369075 | Mgi Jnum | J:310375 |
| Mgi Id | MGI:6762941 | Doi | 10.1111/j.1600-0854.2012.01348.x |
| Citation | Durieux AC, et al. (2012) A centronuclear myopathy--dynamin 2 mutation impairs autophagy in mice. Traffic 13(6):869-79 |
| abstractText | Dynamin 2 (Dnm2) is involved in endocytosis and intracellular membrane trafficking through its function in vesicle formation from distinct membrane compartments. Heterozygous (HTZ) mutations in the DNM2 gene cause dominant centronuclear myopathy or Charcot-Marie-Tooth neuropathy. We generated a knock-in Dnm2R465W mouse model expressing the most frequent human mutation and recently reported that HTZ mice progressively developed a myopathy. We investigated here the cause of neonatal lethality occurring in homozygous (HMZ) mice. We show that HMZ mice present at birth with a reduced body weight, hypoglycemia, increased liver glycogen content and hepatomegaly, in agreement with a defect in neonatal autophagy. In vitro studies performed in HMZ embryonic fibroblasts point out to a decrease in the autophagy flux prior to degradation at the autolysosome. We show that starved HMZ cells have a higher number of immature autophagy-related structures probably due to a defect of acidification. Our results highlight the role of Dnm2 in the cross talk between endosomal and autophagic pathways and evidence a new role of Dnm2-dependent membrane trafficking in autophagy which may be relevant in DNM2-related human diseases. |
