Myotubes are syncytial cells generated by fusion of myoblasts. Among the numerous nuclei in myotubes of skeletal muscle fibres, the majority are equidistantly positioned at the periphery, except for clusters of multiple nuclei underneath the motor endplate. The correct positioning of nuclei is thought to be important for muscle function and requires nesprin-1 (also known as SYNE1), a protein of the nuclear envelope. Consistent with this, mice lacking functional nesprin-1 show defective nuclear positioning and present aspects of Emery–Dreifuss muscular dystrophy. In this study, we perform small interfering RNA (siRNA) experiments in C2C12 myoblasts undergoing differentiation, demonstrating that the positioning of nuclei requires PCM-1, a protein of the centrosome that relocalizes to the nuclear envelope at the onset of differentiation in a manner that is dependent on the presence of nesprin-1. PCM-1 itself is required for recruiting proteins of the dynein–dynactin complex and of kinesin motor complexes. This suggests that microtubule motors that are attached to the nuclear envelope support the movement of nuclei along microtubules, to ensure their correct positioning in the myotube.
The authors declare no competing or financial interests.
A.E.G. and V.D. designed and carried out experiments, and co-wrote the manuscript; C.C. carried out experiments and analysed data; L.E. analysed data and co-wrote the manuscript; A.M. supervised the project, designed and carried out experiments, and co-wrote the manuscript.
The project was supported in part by the Association Française contre les Myopathies (12471, 14810 and 1481).
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.191767.supplemental
- Received May 3, 2016.
- Accepted September 26, 2016.
- © 2016. Published by The Company of Biologists Ltd