Muscle regulates mTOR dependent axonal local translation in motor neurons via CTRP3 secretion: Implications for a neuromuscular disorder, spinal muscular atrophy

Wiebke A. Rehorst, Maximilian P. Thelen, Hendrik Nolte, Clara Türk, Sebahattin Cirak, Jonathan M. Peterson, G. William Wong, Brunhilde Wirth, Marcus Krüger, Dominic Winter, Min Jeong Kye

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Article number154
JournalActa Neuropathologica Communications
Issue number1
StatePublished - Oct 15 2019



  • CTRP3
  • Motor neuron disease
  • Muscle secretome
  • Neuronal protein synthesis
  • SMN (survival motor neuron)
  • Spinal muscular atrophy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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