Morphological and functional remodelling of the neuromuscular junction by skeletal muscle PGC-1α

Anne-Sophie Arnold, Jonathan Gill, Martine Christe, Rocío Ruiz, Shawn McGuirk, Julie St-Pierre, Lucía Tabares and Christoph Handschin ()
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Anne-Sophie Arnold: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland
Jonathan Gill: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland
Martine Christe: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland
Rocío Ruiz: School of Medicine University of Seville, Avda. Sánchez Pizjuan 4, 41009 Sevilla, Spain
Shawn McGuirk: Rosalind and Morris Goodman Cancer Centre, McGill University, 3655 promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6
Julie St-Pierre: Rosalind and Morris Goodman Cancer Centre, McGill University, 3655 promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6
Lucía Tabares: School of Medicine University of Seville, Avda. Sánchez Pizjuan 4, 41009 Sevilla, Spain
Christoph Handschin: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract The neuromuscular junction (NMJ) exhibits high morphological and functional plasticity. In the mature muscle, the relative levels of physical activity are the major determinants of NMJ function. Classically, motor neuron-mediated activation patterns of skeletal muscle have been thought of as the major drivers of NMJ plasticity and the ensuing fibre-type determination in muscle. Here we use muscle-specific transgenic animals for the peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) as a genetic model for trained mice to elucidate the contribution of skeletal muscle to activity-induced adaptation of the NMJ. We find that muscle-specific expression of PGC-1α promotes a remodelling of the NMJ, even in the absence of increased physical activity. Importantly, these plastic changes are not restricted to post-synaptic structures, but extended to modulation of presynaptic cell morphology and function. Therefore, our data indicate that skeletal muscle significantly contributes to the adaptation of the NMJ subsequent to physical activity.

Date: 2014
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DOI: 10.1038/ncomms4569

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