Defective tubulation associated with the myopathy causing S619L DNM2 mutation
- Authors
- Gibbs, E.M., Davidson, A.E., Telfer, W.R., Feldman, E.L., and Dowling, J.J.
- ID
- ZDB-PUB-131119-19
- Date
- 2014
- Source
- Disease models & mechanisms 7(1): 157-61 (Journal)
- Registered Authors
- Dowling, Jim
- Keywords
- Dynamin-2, Excitation-contraction coupling, Myopathy
- MeSH Terms
-
- Plasmids/metabolism
- Muscle, Skeletal/embryology
- Muscle, Skeletal/metabolism
- Muscle, Skeletal/ultrastructure
- Protein Structure, Tertiary
- Zebrafish/embryology
- Animals
- Phenotype
- Dynamin II/genetics*
- Muscular Diseases/genetics*
- Green Fluorescent Proteins/metabolism
- Calcium/metabolism
- Mutation*
- Chlorocebus aethiops
- COS Cells
- PubMed
- 24135484 Full text @ Dis. Model. Mech.
DNM2 is a ubiquitously expressed GTPase that regulates multiple subcellular processes. Mutations in DNM2 are a common cause of centronuclear myopathy, a severe disorder characterized by altered skeletal muscle structure and function. The precise mechanisms underlying disease-associated DNM2 mutations are unresolved. We examined the common DNM2-S619L mutation using both in vitro and in vivo approaches. Expression of DNM2-S619L in zebrafish led to accumulation of aberrant vesicular structures and to defective excitation-contraction coupling. Expression of DNM2-S619L in COS7 cells resulted in defective BIN1-dependent tubule formation. These data suggest that DNM2-S619L may cause disease, in part, by interfering with membrane tubulation.
