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Sculpting the neuronal intracellular environment: from single molecule behavior to local signal integration
Sculpting the neuronal intracellular environment: from single molecule behavior to local signal integration

開催日 2014/9/12
時間 9:00 - 11:00
会場 Room B(501)
Chairperson(s) 合田 裕紀子 / Yukiko Goda (理化学研究所 脳科学総合研究センター シナプス可塑性・回路制御研究チーム / RIKEN, Brain Science Institute, Japan)
瀬藤 光利 / Mitsutoshi Setou (浜松医科大学 解剖学講座 細胞生物学分野 / Department of Cell Biology and Anatomy Hamamatsu University School of Medicine, Japan)

ポリグルタミン酸化酵素 Ttll1 と Ttll7が無いと神経細糸の分布に異常が起きる
Abnormal neurofilament distribution without polygultamylases Ttll1 and Ttll7

  • S2-B-1-5
  • 瀬藤 光利 / Mitsutoshi Setou:1 
  • 1:浜松医科大学 / Hamamatsu University School of Medicine, Japan 

Neronal cytoskeleton are sculpting neuronal structures and functions. There are three major neuronal cytoskeletal systems, microtubules, microfilaments, and neurofilaments. Microtubules are consist of tubulins which are highly polyglutamylated in neurons. We, along with another group, recently revealed that a part of tubulin tyrosine ligase-like (TTLL) proteins catalyses these tubulin polyglutamylation. To elucidate the in vivo function of TTLLs, we generated Ttll1 knockout mice and Ttll7 knockout mice. Ttll1 knockout mice showed very close phenotype to the ROSA22 mice which is a mutant of the other subunit of Ttll1 complex (Loss of alpha-tubulin polyglutamylation in ROSA22 mice is associated with abnormal targeting of KIF1A and modulated synaptic function. Ikegami et al., PNAS2007). We found that Ttll1-Ttll7 double-knockout mice, showed much severe decrease in neuronal polyglutamylation than Ttll1 single knockout mice. Unexpectedly, optical and electron microscopic analyses showed significantly less neurofilaments in dendrites of cortical neurons in the Ttll1-Ttll7 double-knockout mice than those of wild type mice. Single-knockout mice of Ttll1 or Ttll7 did not show this phenotype. The distributions of microtubules and microfilaments in both dendrites and axons were comparable to that of the wild type. These results revealed the novel cytoskeletal regulation in the brain.

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