Myostatin-like proteins regulate synaptic function and neuronal morphology.
Hrvoje Augustin,Hrvoje Augustin,Kieran McGourty,Joern R. Steinert,Helena M. Cochemé,Jennifer Adcott,Jennifer Adcott,Melissa Cabecinha,Alec J. Vincent,Els F. Halff,Josef T. Kittler,Emmanuel Boucrot,Linda Partridge,Linda Partridge +13 more
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TL;DR: 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, highlighting a key role for these proteins in synapse function and neuronal growth.
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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.
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Citations
Myostatin inhibition in combination with antisense oligonucleotide therapy improves outcomes in spinal muscular atrophy
Haiyan Zhou,Jinhong Meng,Alberto Malerba,F. Catapano,Palittiya Sintusek,Palittiya Sintusek,Susan Jarmin,Lucy Feng,Ngoc Lu-Nguyen,Lianwen Sun,Virginie Mariot,Julie Dumonceaux,Jennifer E. Morgan,Paul Gissen,Paul Gissen,George Dickson,Francesco Muntoni,Francesco Muntoni +17 more
TL;DR: The potential of a combinatorial therapy by modulating SMN production and muscle‐enhancing approach as a novel therapeutic strategy for SMA is explored.
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The influence of GDF11 on brain fate and function.
Marissa J. Schafer,Nathan K. LeBrasseur +1 more
- 07 Feb 2019
TL;DR: In the aged brain, exogenous, peripherally delivered GDF11 may enhance neurogenesis and angiogenesis, as well as improve neuropathological outcomes, and its manipulation may improve aspects of brain health in older organisms.
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Mechanism of threshold size assessment: Metamorphosis is triggered by the TGF-beta/Activin ligand Myoglianin.
Lorrie L He,Sara Hyun Joo Shin,Zhou Wang,Isabelle Yuan,Ruthie Weschler,Allie Chiou,Takashi Koyama,H. Frederik Nijhout,Yuichiro Suzuki +8 more
TL;DR: It is proposed that increasing levels of Myo produced by the growing tissues allow larvae to assess their body size and trigger metamorphosis at the threshold size.
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Body Size and Tissue-Scaling Is Regulated by Motoneuron-Derived Activinß in Drosophila melanogaster.
TL;DR: It is reported that loss-of-function mutations in Drosophila Activinβ (Actβ), a member of the TGF-β superfamily, lead to the production of small larvae/pupae and undersized rare adult escapers and the importance of these findings in coordinating proportional scaling of insect muscle mass to appendage size is discussed.
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Muscle-derived Myoglianin regulates Drosophila imaginal disc growth.
TL;DR: It is demonstrated that Myoglianin (Myo), an Activin family member, and a close homolog of mammalian Myostatin (Mstn), is a muscle-derived extrinsic factor that uses canonical dSmad2-mediated signaling to regulate wing size and proposed that Myo is a myokine that helps mediate an allometric relationship between muscles and their associated appendages.
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TL;DR: Results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth, which is significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass.
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Improved structure, function and compatibility for CellProfiler
Lee Kamentsky,Thouis R. Jones,Adam Fraser,Mark-Anthony Bray,David J. Logan,Katherine L. Madden,Vebjorn Ljosa,Curtis Rueden,Kevin W. Eliceiri,Anne Carpenter +9 more
TL;DR: CellProfiler 2.0 is described, which has been engineered to meet the needs of its growing user base, with new algorithms and features to facilitate high-throughput work.
Regulation of muscle mass by myostatin
TL;DR: The existence of circulating tissue-specific growth inhibitors of this type was hypothesized over 40 years ago to explain how sizes of individual tissues are controlled and skeletal muscle appears to be the first example of a tissue whose size is controlled by this type of regulatory mechanism.
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