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

M. Nawa, E. Kage-Nakadai, S. Aiso, K. Okamoto, S. Mitani, M. Matsuoka

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13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1398-1407
Number of pages10
JournalCell Death and Differentiation
Volume19
Issue number8
DOIs
Publication statusPublished - 2012 Aug 1

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Keywords

  • ALS
  • Caenorhabditis elegans
  • FUS
  • TDP-43
  • motor neuron death

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Nawa, M., Kage-Nakadai, E., Aiso, S., Okamoto, K., Mitani, S., & Matsuoka, M. (2012). Reduced expression of BTBD10, an Akt activator, leads to motor neuron death. Cell Death and Differentiation, 19(8), 1398-1407. https://doi.org/10.1038/cdd.2012.19