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Updated: May 6, 2026
Analysis of Embryonic and Larval Zebrafish Skeletal Myofibers from Dissociated Preparations
Published on: November 13, 2013
The myopathy-causing mutation DNM2-S619L leads to defective tubulation in vitro and in developing zebrafish
Elizabeth M Gibbs1, Ann E Davidson, William R Telfer
1Department of Neuroscience, University of Michigan Medical Center, Ann Arbor, MI 48109-2200, USA.
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.
Insights
The dynamin 2 (DNM2)-S619L mutation disrupts cellular membrane tubulation, leading to muscle defects. This finding helps explain how DNM2 mutations cause centronuclear myopathy.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Dynamin 2 (DNM2) is a GTPase involved in various cellular functions.
- Mutations in DNM2 are linked to centronuclear myopathy, a serious muscle disorder.
- The exact mechanisms of DNM2-related myopathies are not fully understood.
Purpose of the Study:
- To investigate the functional impact of the common DNM2-S619L mutation.
- To elucidate the molecular mechanisms by which DNM2 mutations cause disease.
Main Methods:
- In vitro studies using COS7 cells.
- In vivo studies using zebrafish models.
- Analysis of cellular structures and physiological functions.
Main Results:
- DNM2-S619L expression in zebrafish caused aberrant vesicular structures and impaired excitation-contraction coupling.
- DNM2-S619L expression in COS7 cells led to defective BIN1-dependent tubule formation.
- The mutation interferes with essential membrane tubulation processes.
Conclusions:
- The DNM2-S619L mutation contributes to centronuclear myopathy by disrupting membrane tubulation.
- Understanding these mechanisms could inform future therapeutic strategies for muscle disorders.
