Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation
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Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation. / Mills, Richard; Taylor-Weiner, Hermes; Correia, Jorge C; Agudelo, Leandro Z; Allodi, Ilary; Kolonelou, Christina; Martinez-Redondo, Vicente; Ferreira, Duarte M S; Nichterwitz, Susanne; Comley, Laura H; Lundin, Vanessa; Hedlund, Eva; Ruas, Jorge L; Teixeira, Ana I.
I: Molecular Metabolism, Bind 7, 2018, s. 12-22.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation
AU - Mills, Richard
AU - Taylor-Weiner, Hermes
AU - Correia, Jorge C
AU - Agudelo, Leandro Z
AU - Allodi, Ilary
AU - Kolonelou, Christina
AU - Martinez-Redondo, Vicente
AU - Ferreira, Duarte M S
AU - Nichterwitz, Susanne
AU - Comley, Laura H
AU - Lundin, Vanessa
AU - Hedlund, Eva
AU - Ruas, Jorge L
AU - Teixeira, Ana I
N1 - Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Animals
KW - Cells, Cultured
KW - Mice
KW - Motor Neurons/cytology
KW - Mouse Embryonic Stem Cells/cytology
KW - Myoblasts/cytology
KW - Neural Stem Cells/cytology
KW - Neurogenesis
KW - Neuromuscular Junction/cytology
KW - Neurturin/metabolism
KW - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
KW - Synaptic Transmission
U2 - 10.1016/j.molmet.2017.11.001
DO - 10.1016/j.molmet.2017.11.001
M3 - Journal article
C2 - 29157948
VL - 7
SP - 12
EP - 22
JO - Molecular Metabolism
JF - Molecular Metabolism
SN - 2212-8778
ER -
ID: 227431599