ZFIN ID: ZDB-PUB-131119-19
Defective tubulation associated with the myopathy causing S619L DNM2 mutation
Gibbs, E.M., Davidson, A.E., Telfer, W.R., Feldman, E.L., and Dowling, J.J.
Date: 2014
Source: Disease models & mechanisms   7(1): 157-61 (Journal)
Registered Authors: Dowling, Jim
Keywords: Dynamin-2, Excitation-contraction coupling, Myopathy
MeSH Terms:
  • Animals
  • COS Cells
  • Calcium/metabolism
  • Chlorocebus aethiops
  • Dynamin II/genetics*
  • Green Fluorescent Proteins/metabolism
  • Muscle, Skeletal/embryology
  • Muscle, Skeletal/metabolism
  • Muscle, Skeletal/ultrastructure
  • Muscular Diseases/genetics*
  • Mutation*
  • Phenotype
  • Plasmids/metabolism
  • Protein Structure, Tertiary
  • Zebrafish/embryology
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.