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Myostatin-like proteins regulate synaptic function and neuronal morphology.
journal contributionposted on 2019-08-20, 14:08 authored by H Augustin, K McGourty, JR Steinert, HM Cochemé, J Adcott, M Cabecinha, A Vincent, EF Halff, JT Kittler, E Boucrot, L Partridge
Growth factors of the TGFβ superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner. Both myostatin and GDF11 affected synapse formation in isolated rat cortical neuron cultures, suggesting an effect on synaptogenesis beyond neuromuscular junctions. We also show that MYO acts in vivo to inhibit synaptic transmission between neurons in the escape response neural circuit of adult flies. Thus, these anti-myogenic proteins act as important inhibitors of synapse function and neuronal growth.
This work was funded by a Wellcome Trust Strategic Award to L.P., by the Max Planck Society and by a Biotechnology and Biological Sciences Research Council David Phillips fellowship (to E.B.)
CitationDevelopment, 144 (13), pp. 2445-2455
- VoR (Version of Record)
PublisherThe Company of Biologists Ltd
NotesSupplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.152975.supplemental
DrosophilaGDF11Muscle sizeMyoglianinMyostatinSynapseAnimalsBody WeightCell ShapeDown-RegulationDrosophila ProteinsDrosophila melanogasterGene SilencingGlycogen Synthase Kinase 3Growth Differentiation FactorsHumansLarvaMuscle CellsNeurogliaNeuromuscular JunctionNeuronsRatsSignal TransductionSynapsesSynaptic TransmissionTransforming Growth Factor beta