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Mol Metab. 2018 Jan;7:12-22. doi: 10.1016/j.molmet.2017.11.001. Epub 2017 Nov 7.

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

Author information

1
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, 171 77, Stockholm, Sweden.
2
Molecular and Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden.
3
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177, Stockholm, Sweden.
4
Molecular and Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, von Eulers väg 8, 171 77, Stockholm, Sweden. Electronic address: jorge.ruas@ki.se.
5
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, 171 77, Stockholm, Sweden. Electronic address: Ana.Teixeira@ki.se.

Abstract

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.

KEYWORDS:

Motor neuron; Myokine; Neurturin; PGC-1α; Skeletal muscle

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