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タイトル: Calpain-dependent disruption of nucleo-cytoplasmic transport in ALS motor neurons
著者: Yamashita, Takenari
Aizawa, Hitoshi
Teramoto, Sayaka
Akamatsu, Megumi
Kwak, Shin
キーワード: Amyotrophic lateral sclerosis
Molecular neuroscience
発行日: 2017年1月3日
出版者: Nature Publishing Group
掲載誌情報: Takenari Yamashita, Hitoshi Aizawa, Sayaka Teramoto, Megumi Akamatsu, Shin Kwak, "Calpain-dependent disruption of nucleo-cytoplasmic transport in ALS motor neurons", Scientific Reports Online Edition: 2017/01/03 (Japan time), doi:10.1038/srep39994.
関連URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/disruption-of-molecule-transport-pathway-between-nucleus-and-cytoplasm-involved-in-als.html
抄録: Nuclear dysfunction in motor neurons has been hypothesized to be a principal cause of amyotrophic lateral sclerosis (ALS) pathogenesis. Here, we investigated the mechanism by which the nuclear pore complex (NPC) is disrupted in dying motor neurons in a mechanistic ALS mouse model (adenosine deaminase acting on RNA 2 (ADAR2) conditional knockout (AR2) mice) and in ALS patients. We showed that nucleoporins (Nups) that constituted the NPC were cleaved by activated calpain via a Ca2+-permeable AMPA receptor-mediated mechanism in dying motor neurons lacking ADAR2 expression in AR2 mice. In these neurons, nucleo-cytoplasmic transport was disrupted, and the level of the transcript elongation enzyme RNA polymerase II phosphorylated at Ser2 was significantly decreased. Analogous changes were observed in motor neurons lacking ADAR2 immunoreactivity in sporadic ALS patients. Therefore, calpain-dependent NPC disruption may participate in ALS pathogenesis, and inhibiting Ca2+-mediated cell death signals may be a therapeutic strategy for ALS.
内容記述: UTokyo Research掲載「核と細胞質間の分子輸送経路の破綻が筋萎縮性側索硬化症に関与」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/disruption-of-molecule-transport-pathway-between-nucleus-and-cytoplasm-involved-in-als.html
UTokyo Research "Disruption of molecule transport pathway between nucleus and cytoplasm involved in ALS" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/disruption-of-molecule-transport-pathway-between-nucleus-and-cytoplasm-involved-in-als.html
URI: http://hdl.handle.net/2261/61310
ISSN: 2045-2322
出現カテゴリ:014 自然科学
11210 学術雑誌論文


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