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

ABSTRACT: OBJECTIVE:We examined whether skeletal muscle overexpression of PGC-1?1 or PGC-1?4 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-1?1 or PGC-1?4, 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-1?1, but not PGC-1?4, increased NMJ formation and size. PGC-1?1 increased muscle secretion of neurturin, which was sufficient and necessary for the effects of muscle PGC-1?1 on NMJ formation. CONCLUSIONS:Our findings indicate that neurturin is a mediator of PGC-1?1-dependent retrograde signaling from muscle to motor neurons.

SUBMITTER: Mills R 

PROVIDER: S-EPMC5784328 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature