Muscle regulates mTOR dependent axonal local translation in motor neurons via CTRP3 secretion: implications for a neuromuscular disorder, spinal muscular atrophy.
Acta Neuropathol Commun
; 7(1): 154, 2019 10 15.
Article
em En
| MEDLINE
| ID: mdl-31615574
ABSTRACT
Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder, which causes dysfunction/loss of lower motor neurons and muscle weakness as well as atrophy. While SMA is primarily considered as a motor neuron disease, recent data suggests that survival motor neuron (SMN) deficiency in muscle causes intrinsic defects. We systematically profiled secreted proteins from control and SMN deficient muscle cells with two combined metabolic labeling methods and mass spectrometry. From the screening, we found lower levels of C1q/TNF-related protein 3 (CTRP3) in the SMA muscle secretome and confirmed that CTRP3 levels are indeed reduced in muscle tissues and serum of an SMA mouse model. We identified that CTRP3 regulates neuronal protein synthesis including SMN via mTOR pathway. Furthermore, CTRP3 enhances axonal outgrowth and protein synthesis rate, which are well-known impaired processes in SMA motor neurons. Our data revealed a new molecular mechanism by which muscles regulate the physiology of motor neurons via secreted molecules. Dysregulation of this mechanism contributes to the pathophysiology of SMA.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Axônios
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Atrofia Muscular Espinal
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Músculo Esquelético
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Adipocinas
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Serina-Treonina Quinases TOR
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Neurônios Motores
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article