Functional analysis of the septin cytoskeleton in developing and mature brain

• Project/Area Number: 24770184
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Nagoya University
• Principal Investigator: AGETA-IHSIHARA Natsumi 名古屋大学, 理学(系)研究科(研究院), 助教 (60547561)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 細胞骨格

Research Abstract

Neurite outgrowth is a vital process for neural network formation in which microtubules and actin filaments play major roles. Previous studies revealed that another class of nucleotide-binding protein polymers of septins is also required for neurite outgrowth. However, the mechanism are unclear. Here we found that depletion of the pivotal septin subunit SEPT7 from cerebrocortical neurons causes hyperacetylation of microtubules and inhibits the outgrowth of both axons and dendrites. The phenotypic similarity between SEPT7 depletion and inhibition of the major tubulin deacetylase HDAC6 allowed the detection of their functional and physical interactions. While HDAC6–acetylated tubulin interaction is unaffected by the association of septins, it is significantly diminished in SEPT7-depleted neurons. These data suggest a novel molecular network in which septins facilitate HDAC6-mediated tubulin deacetylation, thus optimizing microtubule dynamics for neurite outgrowth.

Research Products

• [Journal Article] Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation (2014)
  • Author(s): Ageta-Ishihara, N., Miyata, T., Ohshima, C., Watanabe, M., Sato, Y., Hamamura, Y., Higashijima, T., Mazitschek, R., Bito, H., Kinoshita, M.
  • Journal Title: Nature Commun Volume: 4 Pages: 2532-2532
  • DOI: 10.1038/ncomms3532
  • Peer Reviewed
• [Journal Article] Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation (2013)
  • Author(s): Ageta-Ishihara N、Miyata T、Ohshima C、Watanabe M、Sato Y、Hamamura Y、Higashiyama T、Mazitschek R、Bito H、Kinoshita M
  • Journal Title: Nature Communications Volume: 4 Pages: 2532-2532
  • Peer Reviewed
• [Journal Article] Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson's disease, causes behavioral alterations but not neurodegeneration in mice (2013)
  • Author(s): Ageta-Ishihara N、Yamakado H、Morita T、Hattori S、Takao K、Miyakawa T、Takahashi R、Kinoshita M
  • Journal Title: Molecular brain Volume: 6(1) Pages: 35-35
  • Peer Reviewed
• [Journal Article] Mechanisms for the brain activation via physical exercise (2013)
  • Author(s): Ageta-Ishihara N、Morita T、Yamauchi Y、Kinoshita M
  • Journal Title: 健康医科学 Volume: 28 Pages: 44-45
  • Peer Reviewed
• [Journal Article] セプチンによるドーパミン神経伝達機構の制御 (2013)
  • Author(s): 木下専、上田(石原)奈津実
  • Journal Title: 脳21 Volume: 28 Pages: 40-45
• [Journal Article] Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson's disease, causes behavioral alterations but not neurodegeneration in mice. (2013)
  • Author(s): Ageta-Ishihara N, Yamakado H, Morita T, Hattori S, Takao K, Miyakawa T, Takahashi R, Kinoshita M
  • Journal Title: Molecular brain Volume: 6 Pages: 35-35
  • DOI: 10.1186/1756-6606-6-35
  • Peer Reviewed / Open Access
• [Journal Article] Mechanisms for the brain activation via physical exercise (2013)
  • Author(s): Natsumi Ageta-Ishihara, Takao Morita, Yasuhisa Yamauchi, Makoto Kinoshita
  • Journal Title: 健康医科学 Volume: 28 Pages: 44-51
  • Peer Reviewed
• [Journal Article] セプチンによるドーパミン神経伝達機構の制御 (2013)
  • Author(s): 上田(石原)奈津実, 木下専
  • Journal Title: 脳21 Volume: 16
• [Journal Article] セプチン (2012)
  • Author(s): 上田(石原)奈津実, 木下専
  • Journal Title: 脳科学辞典 Volume: 無
  • Peer Reviewed
• [Presentation] Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation (2013)
  • Author(s): Ageta-Ishihara N、Miyata T、Ohshima C、Watanabe M、Sato Y、Hamamura Y、Higashiyama T、Mazitschek R、Bito H、Kinoshita M
  • Organizer: The American Society for Cell Biology Annual Meeting
  • Place of Presentation: New Orleans
  • Year and Date: 2013-12-16
• [Presentation] Impaired cerebellar ultrastructure and motor coordination in mice that lack a septin-interacting protein BORG4/CDC42EP4 (2013)
  • Author(s): Ageta-Ishihara N、Kinoshita M
  • Organizer: American Society for Cell Biology Annual Meeting, Special Interest Subgroup Meeting"Septins : Membrane organization and cytoskeletal dynamics from bud necks to dendritic spines
  • Place of Presentation: New Orleans
  • Year and Date: 2013-12-09
• [Presentation] セプチン変異マウスを用いた未知の空間学習・記憶メカニズムの探索 (2013)
  • Author(s): 上田(石原)奈津実、澤田明宏、真野善有、増田博紀、西岡朋生、貝淵弘三、高雄啓三、宮川剛、重本隆一、深澤有吾、木下専
  • Organizer: 第36回日本分子生物学会年会ワークショップ
  • Place of Presentation: 神戸
  • Year and Date: 2013-12-04
• [Presentation] Differential clustering of septin subunits beneath specific perisynaptic membrane domains in the cerebellar cortical neurons and glia (2013)
  • Author(s): Kurita H、Fukazawa Y、Ageta-Ishihara N、Shigemoto R、Kinoshita M
  • Organizer: The 6th international neural microcircuit conference
  • Place of Presentation: 岡崎
  • Year and Date: 2013-06-25
• [Presentation] Immuno-EM 3D reconstruction analysis of septin subunits in the cerebellum (2013)
  • Author(s): Kurita H、Fukazawa Y、Ageta-Ishihara N、Shigemoto R、Kinoshita M
  • Organizer: The Fourteenth InternationalMembrane Research Forum
  • Place of Presentation: 京都
  • Year and Date: 2013-03-16
• [Presentation] Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation (2013)
  • Author(s): Ageta-Ishihara N、Ohshima C、Miyata T、Watanabe M、Mazitschek R、Bito H、Kinoshita M
  • Organizer: SNSS 2013
  • Place of Presentation: 大阪
  • Year and Date: 2013-03-10
• [Presentation] Immuno-EM 3D reconstruction analysis of septin subunits in the cerebellum (2013)
  • Author(s): Kurita H、Fukazawa Y、Ageta-Ishihara N、Shigemoto R、Kinoshita M
  • Organizer: Frontiers in Structural Physiology Symposium
  • Place of Presentation: 名古屋
  • Year and Date: 2013-01-22
• [Presentation] Septins facilitate neurite outgrowth through HDAC6-mediated microtubule deacetylation (2012)
  • Author(s): 上田(石原)奈津実、木下専
  • Organizer: 第35回日本分子生物学会年会シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-12
• [Presentation] Septin-dependent microtubule regulation required for the outgrowth of axons and dendrites (2012)
  • Author(s): Ageta-Ishihara N、Kinoshita M
  • Organizer: 第35回日本神経科学大会シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-21
• [Presentation] Impaired cerebellar ultrastructure and motor coordination in mice that lack a septin-interacting protein BORG4/CDC42EP4.
  • Author(s): Ageta-Ishihara N, Kinoshita M.
  • Organizer: American Society for Cell Biology Annual Meeting, Special Interest Subgroup Meeting, シンポジウム(招待講演)
  • Place of Presentation: Ernest N. Morial Convention Center (New Orleans)
  • Invited
• [Presentation] セプチン変異マウスを用いた未知の空間学習・記憶メカニズムの探索
  • Author(s): 上田(石原)奈津実、澤田明宏、真野善有、増田博紀、西岡朋生、貝淵弘三、高雄啓三、宮川剛、重本隆一、深澤有吾、木下専
  • Organizer: 第36回日本分子生物学会年会, ワークショップ(招待講演)
  • Place of Presentation: 神戸ポートアイランド (神戸市)
  • Invited
• [Presentation] Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation
  • Author(s): Ageta-Ishihara N, Miyata T, Ohshima C, Watanabe M, Sato Y, Hamamura Y, Higashiyama T, Mazitschek R, Bito H, Kinoshita M.
  • Organizer: The American Society for Cell Biology Annual Meeting
  • Place of Presentation: Ernest N. Morial Convention Center (New Orleans)
• [Presentation] 連続切片像再構築法によるシナプス近傍の微細形態計測
  • Author(s): 上田(石原)奈津実、木下専
  • Organizer: 名古屋大学クライオ電子顕微鏡セミナー(招待講演)
  • Place of Presentation: 名古屋大学 (愛知県)
  • Invited
• [Presentation] Septins facilitate neurite outgrowth through HDAC6-mediated microtubule deacetylation
  • Author(s): 上田(石原)奈津実、木下専
  • Organizer: 第35回日本分子生物学会年会, シンポジウム
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡（福岡県）
  • Invited
• [Presentation] Septin-dependent microtubule regulation required for the outgrowth of axons and dendrites
  • Author(s): Natsumi Ageta-Ishihara, Makoto Kinoshita
  • Organizer: 第35回日本神経科学大会, シンポジウム
  • Place of Presentation: 名古屋国際会議場（愛知県）
  • Invited
• [Presentation] Biochemical characterization of Ca2+/calmodulin-dependent protein kinase Iγ as an effective regulator for dendritogenesis in developing cortical neurons
  • Author(s): 鈴木敢三, 竹本-木村さやか, 上條諭志, 上田（石原）奈津実, 奥野浩行, 尾藤晴彦
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡（福岡県）
• [Presentation] Immuno-EM 3D reconstruction analysis of septin subunits in the cerebellum.
  • Author(s): Hiroyuki Kurita, Yugo Fukazawa, Natsumi Ageta-Ishihara, Ryuichi Shigemoto, Makoto Kinoshita.
  • Organizer: Frontiers in Structural Physiology Symposium
  • Place of Presentation: 名古屋大学（愛知県）
• [Presentation] Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation
  • Author(s): Natsumi Ageta-Ishihara, Chika Ohshima, Takaki Miyata, Masahiko Watanabe, Ralph Mazitschek, Haruhiko Bito, Makoto Kinoshita
  • Organizer: SNSS 2013
  • Place of Presentation: アイ・アイ・ランド（大阪府）
• [Presentation] Immuno-EM 3D reconstruction analysis of septin subunits in the cerebellum
  • Author(s): Hiroyuki Kurita, Yugo Fukazawa, Natsumi Ageta-Ishihara, Ryuichi Shigemoto, Makoto Kinoshita.
  • Organizer: The Fourteenth InternationalMembrane Research Forum
  • Place of Presentation: 京都大学（京都府）
• [Book] セプチン、生化学辞典
  • Author(s): 上田(石原)奈津実、木下専
  • Publisher: (in press)