Mst-1 deficiency promotes post-traumatic spinal motor neuron survival via enhancement of autophagy flux

J Neurochem. 2017 Oct;143(2):244-256. doi: 10.1111/jnc.14154. Epub 2017 Sep 19.

Abstract

The mammalian Ste20-like kinase 1 (Mst-1) is a serine-threonine kinase and a component of the Hippo tumor suppressor pathway, which reacts to pathologically relevant stress and regulates cell death. However, little is known about its role in spinal cord injury. Here, we found that p-Mst-1, the activated form of Mst-1, was induced in the post-traumatic spinal motor neurons. In vivo evidence demonstrated that Mst-1 deficiency promoted post-traumatic spinal motor neuron survival, Basso mouse scale scores, and synapse survival. Moreover, we found that autophagosome formation and autolysosome degradation enhanced by Mst-1 deficiency were crucial to attenuate the death of injured spinal motor neurons. Taken together, our findings demonstrate that Mst-1 deficiency promotes post-traumatic spinal motor neuron survival via enhancement of autophagy flux.

Keywords: Mst-1; autolysosome degradation; autophagy; hippo signaling; neuroprotection; spinal cord injury.

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Cell Survival / physiology
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Neurons / metabolism*
  • Motor Neurons / pathology
  • Protein Serine-Threonine Kinases / deficiency*
  • Random Allocation
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology

Substances

  • Stk4 protein, mouse
  • Protein Serine-Threonine Kinases