Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
lcsh:Internal medicine
Motor neuron Neurogenesis Neuromuscular Junction Skeletal muscle PGC-1α Motor Neurons/cytology Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism Synaptic Transmission Myoblasts Mice Neural Stem Cells Myokine Journal Article Animals Neuromuscular Junction/cytology lcsh:RC31-1245 Mouse Embryonic Stem Cells/cytology Cells Cultured Motor Neurons Neurturin/metabolism urogenital system Research Support Non-U.S. Gov't Neurturin Mouse Embryonic Stem Cells Neural Stem Cells/cytology Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha nervous system Original Article Myoblasts/cytology |
| Zdroj: | Molecular Metabolism Molecular Metabolism, Vol 7, Iss, Pp 12-22 (2018) Mills, R, Taylor-Weiner, H, Correia, J C, Agudelo, L Z, Allodi, I, Kolonelou, C, Martinez-Redondo, V, Ferreira, D M S, Nichterwitz, S, Comley, L H, Lundin, V, Hedlund, E, Ruas, J L & Teixeira, A I 2018, ' Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation ', Molecular Metabolism, vol. 7, pp. 12-22 . https://doi.org/10.1016/j.molmet.2017.11.001 |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2017.11.001 |
| Popis: | 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. Highlights • A microfluidic device is used to model neuromuscular junction formation. • Muscle expression of PGC-1α1 increases neuromuscular junction formation and size. • Skeletal muscle transduction with PGC-1α4 does not elicit the same responses. • PGC-1α1 promotes neuromuscular junctions by increasing secretion of neurturin. |
| Databáze: | OpenAIRE |
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