RT Journal Article
SR Electronic
T1 Skeletal muscle MACF1 maintains myonuclei and mitochondria localization through microtubules to control muscle functionalities
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 636464
DO 10.1101/636464
A1 Alireza Ghasemizadeh
A1 Emilie Christin
A1 Alexandre Guiraud
A1 Nathalie Couturier
A1 Valérie Risson
A1 Emmanuelle Girard
A1 Christophe Jagla
A1 Cedric Soler
A1 Lilia Laddada
A1 Colline Sanchez
A1 Francisco Jaque
A1 Audrey Garcia
A1 Marine Lanfranchi
A1 Vincent Jacquemond
A1 Julien Gondin
A1 Julien Courchet
A1 Laurent Schaeffer
A1 Vincent Gache
YR 2019
UL http://biorxiv.org/content/early/2019/05/15/636464.abstract
AB 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.