The myopathy-causing mutation DNM2-S619L leads to defective tubulation in vitro and in developing zebrafish

Dis Model Mech. 2014 Jan;7(1):157-61. doi: 10.1242/dmm.012286. Epub 2013 Oct 17.


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 the 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 causes disease, in part, by interfering with membrane tubulation.

Keywords: Dynamin-2; Excitation-contraction coupling; Myopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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


  • Green Fluorescent Proteins
  • Dynamin II
  • Calcium