Reduced expression of BTBD10, an Akt activator, leads to motor neuron death

Cell Death Differ. 2012 Aug;19(8):1398-407. doi: 10.1038/cdd.2012.19. Epub 2012 Mar 2.

Abstract

BTBD10, an Akt interactor, activates Akt by decreasing the protein phosphatase 2A-mediated dephosphorylation and inactivation of Akt. Overexpression of BTBD10 suppresses motor neuron death that is induced by a familial amyotrophic lateral sclerosis (ALS)-linked superoxide dismutase 1 (SOD1) mutant, G93A-SOD1 in vitro. In this study, we further investigated the BTBD10-mediated suppression of motor neuron death. We found that the small interfering RNA-mediated inhibition of BTBD10 expression led to the death of cultured motor neurons. In Caenorhabditis elegans (C. elegans), disruption of the btbd-10 gene caused not only loss of neurons, including both motor and touch-receptor neurons, but also a locomotion defect. In addition, we found that the expression of BTBD10 was generally decreased in the motor neurons from patients of sporadic ALS and transgenic mice overexpressing G93A-SOD1 (G93A-SOD1-transgenic mice). Collectively, these results suggest that the reduced expression of BTBD10 leads to motor neuron death both in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Cell Death / physiology
  • Gene Silencing
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Transgenic
  • Motor Neurons / cytology*
  • Motor Neurons / metabolism*
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*

Substances

  • BTBD10 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-akt