Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation
Research output: Contribution to journal › Journal article › peer-review
- Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation
Final published version, 2.26 MB, PDF document
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.
|Number of pages||11|
|Publication status||Published - 2018|
Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.
- 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
Number of downloads are based on statistics from Google Scholar and www.ku.dk