title: The myopathy-causing mutation DNM2-S619L leads to defective tubulation in vitro and in developing zebrafish.
abstract: 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.
authors.affiliation: Department of Neuroscience, University of Michigan Medical Center, Ann Arbor, MI 48109-2200, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Gibbs
authors.forename: Ann E
authors.initials: AE
authors.lastname: Davidson
authors.forename: William R
authors.initials: WR
authors.lastname: Telfer
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
authors.forename: James J
authors.initials: JJ
authors.lastname: Dowling
mesh_terms: D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002522:Chlorocebus aethiops; D034285:Dynamin II / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D009135:Muscular Diseases / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015027:Zebrafish / Q000196:embryology
chemical_list: D049452:Green Fluorescent Proteins; D034285:Dynamin II; D002118:Calcium
keywords: Dynamin-2; Excitation-contraction coupling; Myopathy