Analysis of a Novel Protein Shootin1, which is involved in organization of an asymmetric signal for neuronal polarization

• Project/Area Number: 18300107
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: INAGAKI Naoyuki Nara Institute of Science and Technology, Biological Sciences, Associate Professor (20223216)
• Co-Investigator(Kenkyū-buntansha): SHIMADA Tadayuki Nara Institute of Science and Technology, Biological Sciences, Assistant Professor (80379552)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥2,160,000); Fiscal Year 2007: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000); Fiscal Year 2006: ¥7,800,000 (Direct Cost: ¥7,800,000)
• Keywords: Neuron / Cell polarity / Axon / Dendrite / Shootin1 / L1 / Actin / Growth cone / Shootin1 / Wave / PI 3-kinase / ノックアウトマウス

Research Abstract

The basic function of neurons is to receive, integrate and transmit signals. To do so, most neurons develop polarity by forming a single axon and multiple dendrites. Neurons have the remarkable ability to polarize even in symmetrical in vitro environments. Although recent studies have shown that asymmetric intracellular signals can induce neuronal polarization, it remains unclear how these polarized signals are organized without asymmetric cues. We recently described an intracellular protein, shootin1, which plays a critical role in neuronal polarization. During the symmetry breaking step, shootin1 becomes up-regulated, undergoes a fluctuating accumulation in growth cones at neurite tips, and eventually accumulates asymmetrically in a single growth cone. Accumulation of shootin1 in nerve growth cones also enhanced neurite elongation. In this study, we examined molecular mechanisms for shootin1-induced neurite outgrowth and the mechanisms for generation of asymmetric signal of shootin1. Shootin1 not only acted as a upstream regulator of PI 3-kinase but also enhanced neurite elongation, by linking a cell adhesion molecule Ll-CAM to actin filament retrograde flow as a "clutch molecule". We also obtained data to suggest that positive feedback amplification of shootin1 signal in growth cones contributes to generation of asymmetric shootin 1 signals during neuronal polarization. We also succeeded in generation of shootin 1 knockout mice, and are currently analyzing their phenotypes.

Research Products

• [Journal Article] Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon outgrowth (2008)
  • Author(s): Shimada, T., Toriyama, M., Uemura, K., Kamiguchi, H., Sugiura, T., Watanabe, N. and Inagaki, N.
  • Journal Title: J. Cell Biol. (印刷中)
  • NAID: 120005830838
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon outgrowth (2008)
  • Author(s): Shimada, T., Toriyama, M., Uemura, K., Kamiguchi, H., Sugiura, T., Watanabe, N., Inagaki, N
  • Journal Title: J. Cell Biol (in press)
  • NAID: 120005830838
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Neuronal Process Outgrowth (2008)
  • Author(s): Mori, T., Inagaki, N., Kamiguchi, H
  • Journal Title: Handbook of Neurochemistry and Molecular Neurobiology, Springer-Verlag, Berlin (Lajtha F.W. (ed)) (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Singar1, a Novel RUN Domain-containing Protein, Suppresses Formation of Surplus Axons for Neuronal Polarity. (2007)
  • Author(s): Mori, T., Wada, T., Suzuki, T., Kubota, Y. and Inagaki, N.
  • Journal Title: J. Biol. Chem. 282 Pages: 19884-19893
  • NAID: 120005830839
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 神経極性形成とShootin1のフィードバックループ (2007)
  • Author(s): 稲垣直之、鳥山道則、島田忠之
  • Journal Title: 生化学 79 Pages: 799-802
  • NAID: 10019550731
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Preferential localization of rat GAPDS on the ribs of fibrous sheath of sperm flagellum and its expression during flagellar formation (2007)
  • Author(s): Tanii I., et. al.
  • Journal Title: Acta Histochem. Cytochem. 40 Pages: 19-26
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Shootin1による神経細胞の対称性破壊と極性形成 (2007)
  • Author(s): 稲垣直之、鳥山道則、島田忠之
  • Journal Title: 脳21 10 Pages: 107-109
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Singar1 a novel RUN domain-containing protein, suppresses formation of surplus axons for neuronal polarity (2007)
  • Author(s): Mori, T., Wada, T., Suzuki, T, Kubota, Y., Inagaki, N
  • Journal Title: J. Biol. Chem 282 Pages: 19884-19893
  • NAID: 120005830839
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Preferential Localization of Rat GAPDS on the ribs of fibrous sheath of sperm flagellum and its expression during flagellar formation (2007)
  • Author(s): Tanii, I, Yagura, T, Inagaki, N, Nakayama, T, Imaizumi, K, Yoshinaga, K
  • Journal Title: Acta Histochem Cytochem 40 Pages: 19-26
  • NAID: 110006633410
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Neuronal polarity formation and feedback loop of shootin1 (2007)
  • Author(s): Inagaki, N., Toriyama, M., Shimada, T
  • Journal Title: Seikagaku 79 Pages: 799-802
  • NAID: 10019550731
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Neuronal symmetry breaking and polarity formation by shoootin1 (2007)
  • Author(s): Inagaki, N., Toriyama, M., Shimada, T
  • Journal Title: Nou 21 10 Pages: 107-109
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Preferential localization of rat GAPDS on the ribs of fibrous sheath of sperm flagellum and its expression during flagellar formation (2007)
  • Author(s): Tanii I., et al.
  • Journal Title: Acta Histochem. Cytochem. 40 Pages: 19-26
• [Journal Article] Shootin 1による神経細胞の対称性破壊と極性形成 (2007)
  • Author(s): 稲垣直之, 鳥山道則, 島田忠之
  • Journal Title: 脳21 10 Pages: 107-109
• [Journal Article] Shootinl:a protein involved in organization of an asymmetric signal for neuronal polarization (2006)
  • Author(s): Toriyama M. Shimada T., Kim K.B., Mitsuba M., Nomura E., Katsuta K., Sakumura Y., Roepstorff P., Inagaki N.,
  • Journal Title: J. Cell Biol. 175 Pages: 147-157
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Proteomic identification of a novel isoform of collapsin response mediator protein(CRMP-2)in spinal nerves peripheral to dorsal root ganglia (2006)
  • Author(s): Katano T., et. al.
  • Journal Title: Proteomics 6 Pages: 6085-6094
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Vimentin-Ser82 as a memory phosphorylation site in astrocyte (2006)
  • Author(s): Oguri T., et. al.
  • Journal Title: Genes to Cells 11 Pages: 531-540
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Shootin1: a protein involved in organization of an asymmetric signal for neuronal polarization (2006)
  • Author(s): Toriyama, M. Shimada, T., Kim, K.B., Mitsuba, M., Nomura, E, Katsuta, K., Sakumura, Y., Roepstorff, P., Inagaki, N
  • Journal Title: J. Cell Biol 175 Pages: 147-157
  • NAID: 120005830840
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Proteomic identification of a novel isoform of collapsin response mediator protein (CRMP-2) in spinal nerves peripheral to dorsal root ganglia (2006)
  • Author(s): Katano, T., Mabuchi, T., Okuda-Ashitaka, E., Inagaki, N., Kinumi, T., Ito, S
  • Journal Title: Proteomics 8 Pages: 6085-6094
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Vimentin-Ser82 as a memory phosphorylation site in astrocytes (2006)
  • Author(s): Oguri, T., Inoko, A., Shima, H., Izawa, H., Arimura, N., Yamaguchi, T., Inagaki, N., Kaibuchi, K., Kikuchi, K., Inagaki, M
  • Journal Title: Genes to Cells 11 Pages: 531-540
  • NAID: 120000961744
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Shootin 1 : a protein involved in organization of an asymmetric signal for neuronal polarization (2006)
  • Author(s): Toriyama M., et al.
  • Journal Title: J. Cell Biol. 175 Pages: 147-157
• [Journal Article] Proteomic identification of a novel isoform of collapsin response mediator protein (CRMP-2) in spinal nerves peripheral to dorsal root ganglia (2006)
  • Author(s): Katano T., et al.
  • Journal Title: Proteomics 6 Pages: 6085-6094
• [Journal Article] Vimentin-Ser82 as a memory phosphorylation site in astrocyte (2006)
  • Author(s): Oguri T., et al.
  • Journal Title: Genes to Cells 11 Pages: 531-540
• [Presentation] 新規タンパク質Shootin1とSingar1による神経極性形成の制御 (2007)
  • Author(s): 稲垣直之、鳥山道則、島田忠之、森達也
  • Organizer: 第30回日本分子生物学会・第80回日本生化学会合同大会ワークショップ、From shape to function:ニューロンの形態形成と可塑性を司る分子基盤
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Shootin1と神経突起伸長のPositive feedback loopによる神経極性形成機構 (2007)
  • Author(s): 鳥山道則、作村諭一、浅野卓也、島田忠之、稲垣直之
  • Organizer: 第30回日本分子生物学会・第80回日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 新規タンパク質Shootin1は、F-actinの求心的移動とL1-CAMを連結することで神経突起伸長を促進する (2007)
  • Author(s): 島田忠之、鳥山道則、上口裕之、杉浦忠男、渡邊直樹、稲垣直之
  • Organizer: 第30回日本分子生物学会・第80回日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 新規タンパク質Shootin1とSingar1による神経極性形成の制御 (2007)
  • Author(s): 稲垣直之、鳥山道則、島田忠之、森達也
  • Organizer: 第30回 日本分子生物学会・第80回 日本生化学会合同大会ワークショップ、From shape to function:ニューロンの形態形成と可塑性を司る分子基盤
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] Shootin1と神経突起伸長のPositive feedback loopによる神経極性形成機構 (2007)
  • Author(s): 鳥山道則、作村諭一、浅野卓也、島田忠之、稲垣直之
  • Organizer: 第30回 日本分子生物学会・第80回 日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 新規タンパク質Shootin1は、F-actinの求心的移動とL1-CAMを連結することで神経突起伸長を促進する (2007)
  • Author(s): 島田忠之、鳥山道則、上口裕之、杉浦忠男、渡邊直樹、稲垣直之
  • Organizer: 第30回 日本分子生物学会・第80回 日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] プロテオミクスを用いた脳神経回路網形成の分子機構の解析 (2007)
  • Author(s): 稲垣直之
  • Organizer: 第57回日本電気泳動学会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2007-06-20
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Proteomic analysis of neuronal network formation (2007)
  • Author(s): Inagaki, N
  • Organizer: 57th Symposium of Japanese Society for Electrophoresis
  • Place of Presentation: Yokohama
  • Year and Date: 2007-06-20
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] プロテオミクスを用いた脳神経回路網形成の分子機構の解析 (2007)
  • Author(s): 稲垣直之
  • Organizer: 第57回 日本電気泳動学会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2007-06-20
• [Presentation] Shootin1 Transmits Driving Force of F-actin Flow to L1-CAM for Neurite Elongation (2007)
  • Author(s): Shimada, T., Toriyama, M., Uemura K., Sugiura, T., Watanabe, N., Kamiguchi, H., and Inagaki, N.
  • Organizer: 47th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: Washington DC, USA
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Quantitative Analysis of Shootin1 and neurite elongation (2007)
  • Author(s): Asano, T., Toriyama, M., Inagaki, N., Sakumura, Y., Ishii, S.
  • Organizer: Neuro2007第30回日本神経科学大会
  • Place of Presentation: 横浜
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Regulation of neuronal polarity formation by novel proteins shootin1 and singar1 (2007)
  • Author(s): Inagaki, N., Toriyama, M., Shimada, T., Mori, T
  • Organizer: Biochemistry and Molecular Bioloby (BMB) 2007
  • Place of Presentation: Yokohama
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Neuronal polarity formation by feedback interaction between shoootin1 and neurite length (2007)
  • Author(s): Toriyama, M., Sakumura, Y., Asano, T., Shimada, T., Inagaki, N
  • Organizer: Biochemistry and Molecular Bioloby (BMB) 2007
  • Place of Presentation: Yokohama
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Shootin1 interacts with actin retrograde flow and Ll-CAM to promote axon outgrowth (2007)
  • Author(s): Shimada, T., Toriyama, M., Kamiguchi, H., Sugiura, T., Watanabe, N., Inagaki, N
  • Organizer: Biochemistry and Molecular Bioloby (BMB) 2007
  • Place of Presentation: Yokohama
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Shootin1 Transmits Driving Force of F-actin Flow to Ll-CAM for Neurite Elongation (2007)
  • Author(s): Shimada, T., Toriyama, M., Uemura, K., Sugiura, T., Watanabe, N., Kamiguchi, H., Inagaki, N
  • Organizer: 47th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: Washington DC, USA
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Quantitative Analysis of Shootin1 and neurite elongation (2007)
  • Author(s): Asano, T., Toriyama, M., Inagaki, N., Sakumura, Y., Ishii, S
  • Organizer: Neuro2007
  • Place of Presentation: Yokohama
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Quantitative Analysis of Shootin1 and neurite elongation (2007)
  • Author(s): Asano, T., Toriyama, M., Inagaki, N., Sakumura, Y., Ishii, S.
  • Organizer: Neuro2007 第30回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Singar a Novel Protein that Suppresses Formation of Surplus Axons for Neuronal Polarization (2006)
  • Author(s): Mori, T., Wada, T., Suzuki, T., Inagaki, N.
  • Organizer: Cold Spring Harbor Meeting on Axon Guidance, Synaptogenesis & Neural Plasticity
  • Place of Presentation: New York, USA.
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Shootin1 Transmits Driving Force of F-actin Flow to L1-CAM for Neurite Elongation (2006)
  • Author(s): Shimada, T., Toriyama, M., Uemura K., Sugiura, T., Watanabe, N., Kamiguchi, H., Lemmon, V., and Inagaki, N.
  • Organizer: Cold Spring Harbor Meeting on Axon Guidance, Synaptogenesis & Neural Plasticity
  • Place of Presentation: New York, USA.
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Identification of Singar, a novel protein which suppresses the formation of surplus axons (2006)
  • Author(s): Mori T, Wada T, Suzuki, Inagaki N.
  • Organizer: 第29回日本神経科学大会
  • Place of Presentation: 京都
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Shootin1 is involved in spontaneous neuronal polarity formation (2006)
  • Author(s): Toriyama, M., Shimada, T., Kim, K.B., Mitsuba, M., Nomura, E., Roepstorff, P., and Inagaki, N.
  • Organizer: 20th IUBMB International, Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto.
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Identification of a novel form of collapsin response mediator protein-2(CRMP-2) in spinal nerves peripheral to dorsal root ganglia by proteomic approach (2006)
  • Author(s): Katano, T., Mabuchi, T., Okuda-Ashitaka, E., Inagaki, N., Kinumi, T., and Ito, S.
  • Organizer: 20th IUBMB International, Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto.
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Singar a Novel Protein that Suppresses Formation of Surplus Axons for Neuronal Polarization (2006)
  • Author(s): Mori, T., Wada, T., Suzuki, T., Inagaki, N
  • Organizer: Cold Spring Harbor Meeting on Axon Guidance, Synaptogenesis & Neural Plasticity
  • Place of Presentation: New York, USA
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Shootin1 Transmits Driving Force of F-actin Flow to Ll-CAM for Neurite Elongation (2006)
  • Author(s): Shimada, T., Toriyama, M., Uemura K., Sugiura, T., Watanabe, N., Kamiguchi, H., Lemmon, V., Inagaki, N
  • Organizer: Cold Spring Harbor Meeting on Axon Guidance, Synaptogenesis & Neural Plasticity
  • Place of Presentation: New York, USA
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Identification of Singar, a novel protein which suppresses the formation of surplus axons (2006)
  • Author(s): Mori, T, Wada, T, Suzuki, Inagaki, N
  • Organizer: 29th Meeting for Japanese Society of Neuroscience
  • Place of Presentation: Kyoto
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Shootin1 is involved in spontaneous neuronal polarity formation (2006)
  • Author(s): Toriyama, M., Shimada, T., Kim, K.B., Mitsuba, M., Nomura, E., Roepstorff, P., Inagaki, N
  • Organizer: 20th IUBMB International, Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Identification of a novel form of collapsin response mediator protein-2 (CRMP-2) in spinal nerves peripheral to dorsal root ganglia by proteomic approach (2006)
  • Author(s): Katano, T., Mabuchi, T., Okuda-Ashitaka, E., Inagaki, N., Kinumi, T., Ito, S
  • Organizer: 20th IUBMB International, Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Neuronal Process Outgrowth., In Lajtha F.W.(ed): Handbook of Neurochemistry and Molecular Neurobiology (2008)
  • Author(s): Mori T., Inagaki N., Kamiguchi H.
  • Publisher: Springer-Verlag, Berlin(印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Neuronal Process Outgrowth., In Lajtha F.W.(ed): Handbook of Neurochemistry and Molecular Neurobiology
  • Author(s): Mori T., Inagaki N., Kamiguchi H.
  • Publisher: Springer-Verlag, Berlin(印刷中)
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://bsw3.naist.jp/itoh/home/oldhome/contents/inagaki/shoukai_inagaki.html
• [Remarks]
  • URL: http://bsw3.naist.jp/itoh/home/oldhome/contents/inagaki/shoukai_inagaki.html
• [Patent(Industrial Property Rights)] Singarの発現または機能の抑制による神経軸索の形成・伸長と神経再生への応用 (2006)
  • Inventor(s): 稲垣直之, 森達也, 小原収, 長瀬隆弘
  • Industrial Property Rights Holder: 奈良先端科学技術際学院大学、かずさDNA研究所
  • Filing Date: 2006-10-26
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] Singarの発現または機能の抑制による神経軸索の形成・伸長と神経再生への応用 (2006)
  • Inventor(s): 稲垣直之, 森達也, 小原収, 長瀬隆弘
  • Industrial Property Rights Holder: 奈良先端科学技術際学院大学, かずさDNA研究所
  • Filing Date: 2006-10-26