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突起伸展・回路形成 2
Axonal/Dendritic Growth and Circuit Formation 2

開催日 2014/9/13
時間 16:00 - 17:00
会場 Room J(313+314)
Chairperson(s) 竹居 光太郎 / Kohtaro Takei (横浜市立大学大学院生命医科学研究科 / Graduate School of Medicine, Life Science, Yokohama City University, Japan)
生沼 泉 / Izumi Oinuma (京都大学大学院生命科学研究科生体システム学 / Laboratory of Molecular Neurobiology, Garduate School of Biostudies, Kyoto University, Japan)

Axonal branching and elongation are independently regulated by cAMP

  • O3-J-4-2
  • 周 至文 / Zhiwen Zhou:1 田中 謙二 / Kenji Tanaka:2 松永 茂 / Shigeru Matsunaga:3 伊関 峰生 / Mineo Iseki:4 渡辺 正勝 / Masakatsu Watanabe:5 松木 則夫 / Norio Matsuki:1 池谷 裕二 / Yuji Ikegaya:1 小山 隆太 / Ryuta Koyama:1 
  • 1:東京大院・薬・薬品作用学 / Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences,The University of Tokyo, Japan 2:慶應大・医・精神神経科学 / Department of Neuropsychiatry, School of Medicine, Keio University, Japan 3:浜松ホトニクス株式会社・中央研究所 / Central Research Laboratory, Hamamatsu Photonics K.K., Japan 4:東邦大・薬・薬品物理分析学 / Faculty of Pharmaceutical Sciences, Toho University, Japan 5:光産業創成大学院大学・光バイオ分野 / The Graduate School for the Creation of New Photonics Industries, Japan 

Axonal branching and elongation are stepwise processes essential for the establishment of functional neural circuits. Previous studies have shown that cAMP plays an important role in regulating axonal outgrowth: however, it remains unclear whether and how cAMP regulates axonal branching and elongation independently. To answer this question, we utilized photoactivated adenylyl cyclase (PAC), which produces cAMP either transiently or continuously depending on the exposure time to the blue light, for regulating the intracellular cAMP levels. In the primary cultures of dentate granule cells transfected with PAC, we found that the 10-min exposure of blue light induced axonal branching but not elongation, whereas the 30-min exposure of blue light induced both axonal branching and elongation. In PAC-expressing granule cells that were exposed to the blue light for 30 min, siRNA-mediated knockdown of protein kinase A (PKA) inhibited axonal branching but not elongation, whereas siRNA-mediated knockdown of exchange protein directly activated by cAMP (EPAC) inhibited axonal elongation but not branching. These results suggest that the intracellular cAMP regulates axonal branching and elongation via PKA and EPAC, respectively. Furthermore, our study indicates that the temporal regulation of the intracellular cAMP levels underlies the independent cAMP cascades-mediated axonal morphogenesis.

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