Myostatin-like proteins regulate synaptic function and neuronal morphology

Hrvoje Augustin, Kieran McGourty, Joern R. Steinert, Helena M. Cochemé, Jennifer Adcott, Melissa Cabecinha, Alec Vincent, Els F. Halff, Josef T. Kittler, Emmanuel Boucrot, Linda Partridge

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2445-2455
Number of pages11
JournalDevelopment (Cambridge)
Volume144
Issue number13
DOIs
Publication statusPublished - 2017
Externally publishedYes

Keywords

  • Drosophila
  • GDF11
  • Muscle size
  • Myoglianin
  • Myostatin
  • Synapse

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