Institut NeuroMyoGène
    Laboratoire Physiopathologie et Génétique du Neurone et du Muscle
    CNRS UMR 5261 -INSERM U1315
    Université de Lyon - Université Claude Bernard Lyon 1
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A new publication is available on bioRxiv!

Skeletal muscle MACF1 maintains myonuclei and mitochondria localization through microtubules to control muscle functionalities
Alireza Ghasemizadeh, Emilie Christin, Alexandre Guiraud, Nathalie Couturier, Valérie Risson, Emmanuelle Girard, Christophe Jagla, Cedric Soler, Lilia Laddada, Colline Sanchez, Francisco Jaque, Audrey Garcia, Marine Lanfranchi, Vincent Jacquemond, Julien Gondin, Julien Courchet, Laurent Schaeffer, Vincent Gache
bioRxiv 636464; doi: https://doi.org/10.1101/636464

Abstract: Skeletal muscle is made from multinuclear myofiber, where myonuclei are positioned at the periphery or clustered below neuromuscular junctions (NMJs). While mispositioned myonuclei are the hallmark of numerous muscular diseases, the molecular machinery maintaining myonuclei positioning in mature muscle is still unknown. Here, we identified microtubule-associated protein MACF1 as an evolutionary conserved regulator of myonuclei positioning, in vitro and in vivo, controlling the “microtubule code” and stabilizing the microtubule dynamics during myofibers maturation, preferentially at NMJs. Specifically, MACF1 governs myonuclei motion, mitochondria positioning and structure and acetylcholine receptors (AChRs) clustering. Macf1-KO in young and adult mice decreases muscle excitability and causes evolutionary myonuclei positioning alterations in adult mice, paralleled with high mitochondria content and improved resistance to fatigue. We present MACF1 as a primary actor of the maintenance of synaptic myonuclei and AChRs clustering, peripheral myonuclei positioning and mitochondria organization through the control of microtubule network dynamics in muscle fibers.


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