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

• Published in: Cell death and differentiation Vol. 19; no. 8; pp. 1398 - 1407
• Main Authors: Nawa, M, Kage-Nakadai, E, Aiso, S, Okamoto, K, Mitani, S, Matsuoka, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2012; Nature Publishing Group
• Subjects: 631/208/199; 631/378/1689/1285; 631/378/1934; 631/80/304; Amyotrophic lateral sclerosis; Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Caenorhabditis elegans; Cell Biology; Cell Cycle Analysis; Cell death; Cell Death - physiology; Gene Silencing; HEK293 Cells; HeLa Cells; Humans; Kinases; Life Sciences; Mice; Mice, Transgenic; Motor Neurons - cytology; Motor Neurons - metabolism; Mutation; Nematodes; Neurons; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; Original Paper; Pathogenesis; Phosphatase; Phosphorylation; Proteins; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Sarcoma; Stem Cells; Transgenic animals; Japan; ALS; motor neuron death; FUS; TDP-43
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2012.19

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 .