Résumé :
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The basic unit of skeletal muscle in metazoans is the multinucleate myofiber, within which individual nuclei are regularly positioned. Improperly positioned nuclei are a hallmark of numerous muscles diseases, including centronuclear myopathies, but it is unclear whether correct nuclear positioning is necessary for muscle function. We performed in vitro time-lapse video microscopy on myotubes to measure nuclei speed and localization in early myotubes. Using a cytoskeleton targeting drugs approach and a siRNA screen on molecular motors, we identified two distinct microtubules dependent nuclei movements in myotubes. The first movement occurs just after fusion: entering nucleus of the myoblast moved towards the center of the myotube. This nuclear movement is driven by dynein/dynactin complex, regulated by Cdc42, Par6 and Par3. The second movement occurs inside the myotube and is responsible for the alignment of nuclei. This nuclear movement is driven by the interaction between a kinesin and the Microtubule Associated Protein Map7. This complex maintains an anti-parallel network of microtubules in myotubes and allows nuclei to correctly align within the myotube. We demonstrate that myonuclear positionings is physiologically important. Our results show for the first time that the ability to correctly position myonuclei correlates with better muscle growth and function. Correcting nuclear positioning defects in patients with muscle diseases might benefit muscle strength and improve muscle function.
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