Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation

Research output: Contribution to journalJournal articlepeer-review

  • Richard Mills
  • Hermes Taylor-Weiner
  • Jorge C Correia
  • Leandro Z Agudelo
  • Allodi, Ilary
  • Christina Kolonelou
  • Vicente Martinez-Redondo
  • Duarte M S Ferreira
  • Susanne Nichterwitz
  • Laura H Comley
  • Vanessa Lundin
  • Eva Hedlund
  • Jorge L Ruas
  • Ana I Teixeira

OBJECTIVE: We examined whether skeletal muscle overexpression of PGC-1α1 or PGC-1α4 affected myokine secretion and neuromuscular junction (NMJ) formation.

METHODS: A microfluidic device was used to model endocrine signaling and NMJ formation between primary mouse myoblast-derived myotubes and embryonic stem cell-derived motor neurons. Differences in hydrostatic pressure allowed for fluidic isolation of either cell type or unidirectional signaling in the fluid phase. Myotubes were transduced to overexpress PGC-1α1 or PGC-1α4, and myokine secretion was quantified using a proximity extension assay. Morphological and functional changes in NMJs were measured by fluorescent microscopy and by monitoring muscle contraction upon motor neuron stimulation.

RESULTS: Skeletal muscle transduction with PGC-1α1, but not PGC-1α4, increased NMJ formation and size. PGC-1α1 increased muscle secretion of neurturin, which was sufficient and necessary for the effects of muscle PGC-1α1 on NMJ formation.

CONCLUSIONS: Our findings indicate that neurturin is a mediator of PGC-1α1-dependent retrograde signaling from muscle to motor neurons.

Original languageEnglish
JournalMolecular Metabolism
Pages (from-to)12-22
Number of pages11
Publication statusPublished - 2018
Externally publishedYes

Bibliographical note

Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

    Research areas

  • Animals, Cells, Cultured, Mice, Motor Neurons/cytology, Mouse Embryonic Stem Cells/cytology, Myoblasts/cytology, Neural Stem Cells/cytology, Neurogenesis, Neuromuscular Junction/cytology, Neurturin/metabolism, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism, Synaptic Transmission

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