Study on a regulatory mechanism of the maturation of dendritic spines and the synaptic plasticity by lipid-related molecules

• Project/Area Number: 23590232
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: University of Fukui
• Principal Investigator: XIE Min-Jue 福井大学, 医学部, 助教 (40444210)
• Co-Investigator(Kenkyū-buntansha): SATO Makoto 大阪大学, 連合小児発達学研究科, 教授 (10222019) ; KURODA Kazuki 福井大学, 医学部, 助教 (60557966) ; IGUCHI Tokuichi 大阪大学, 医学系研究科, 助教 (60509305) ; KOMADA Munekazu 愛知学院大学, 歯学部, 助教 (90523994)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: シナプス形成 / シナプス可塑性 / LL5β / PSD / LTD / 可塑性 / LTP / PIP3

Research Abstract

Synapse function and plasticity depend on the morphology of dendritic spine. Here, we report that Phldb2 (pleckstrin homology-like domain, family B, member 2, LL5beta), one binding partner for a well-known actin-cross-linking protein Filamin A, works as a positive regulator of spine maturation. We generated LL5beta knockout mice and found that a proportion of immature spines (filopodia and thin spines) increased in the hippocampus in vivo, which is consistent with our previous observations with LL5beta knocked-down cultured hippocampal neurons. Next, we asked whether or not LL5beta is involved in synaptic plasticity. We observed that NMDA-induced AMPA receptor endocytosis and low-frequency stimulation-induced long-term depression were blocked in hippocampal neurons of the LL5beta knockout mice. Therefore, it is likely that LL5beta plays an important role for the synaptic plasticity and the maturation of dendritic spines.

Research Products

• [Journal Article] WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration (2013)
  • Author(s): Xie, M.-J., Yagi, H., Kuroda, K., Wang CC., Komada, M., Zhao, H., Sakakibara, A., Miyata, T., Nagata, K., Oka, Y., Iguchi, T. and Sato, M
  • Journal Title: Cereb. Cortex Volume: 23(6) Pages: 1410-1423
  • Peer Reviewed
• [Journal Article] Smoothened controls cyclinD2 expression and regulates the generation ofintermediate progenitors in the developing cortex (2013)
  • Author(s): Komada, M., Iguchi,T., Takeda, T., Ishibashi, M. and Sato, M
  • Journal Title: Neurosci. Lett Volume: 547 Pages: 87-91
  • Peer Reviewed
• [Journal Article] Episodic memory retrieval for story characters in high-functioning autism (2013)
  • Author(s): Komeda, H., Kosaka, H., Saito, N-D., Inohara, K., Munesue, T., Ishitobi, M., Sato, M. and Okazawa, H
  • Journal Title: Molecular Autism Volume: 4(1) Pages: 20-20
  • NAID: 120005293585
  • Peer Reviewed
• [Journal Article] Post-natal treatment by a blood-brain-barrier permeable calpain inhibitor, SNJ1945 rescued defective neuronal migration and neuronal circuit formation in lissencephaly (2013)
  • Author(s): Toba, S., Tamura, Y., Kumamoto, K., Yamada, M., Takao, K., Hattori, S., Miyakawa, T., Kataoka, Y., Azuma, M., Hayasaka, K., Amamoto, M., Tominaga, K., Wynshaw-Boris, A., Wanibuchi, H., Oka, Y., Sato, M., Kato, M. and Hirotsune, S
  • Journal Title: Sci. Rep Volume: 3 Pages: 1224-1224
  • Peer Reviewed
• [Journal Article] Canonical Wnt signaling induces BMP-4 to specify slow myofibrogenesis of embryonic myoblasts (2013)
  • Author(s): Kuroda, K., Kuang, S., Taketo, MM. and Rudnicki, MA
  • Journal Title: Skelet Muscle Volume: 3(1) Pages: 5-5
  • Peer Reviewed
• [Journal Article] WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration (2013)
  • Author(s): Xie, M.-J., Yagi, H., Kuroda, K., Wang C.-C., Komada, M., Zhao, H., Sakakibara, A., Miyata, T., Nagata, K., Oka, Y., Iguchi, T. and Sato, M.
  • Journal Title: Cerebral Cortex Volume: (in press) Issue: 6 Pages: 1410-1423
  • DOI: 10.1093/cercor/bhs123
  • Peer Reviewed
• [Journal Article] Long-term oxytocin administration improves social behaviors in a girl with autistic disorder (2012)
  • Author(s): Kosaka, H., Munesue, T., Ishitobi, M., Asano, M., Omori, M., Sato, M., Tomoda, A. and Wada, Y
  • Journal Title: BMC Psychiatry Volume: 12(1) (case report) Pages: 110-110
  • Peer Reviewed
• [Journal Article] Activation of Aurora-A is essential for neuronal migration via modulation of microtubule organization (2012)
  • Author(s): Takitoh, T., Kumamoto, K., Wang CC., Sato, M., Toba, S., Wynshaw-Boris, A., and Hirotsune, S
  • Journal Title: J . Neurosci Volume: 32(32) Pages: 11050-11066
  • Peer Reviewed
• [Journal Article] Effects of antidepressants and mood stabilizers on serum levels of adiponectin (2012)
  • Author(s): Omata, N., Murata, T., Narita, K., Maruoka, N., Mitsuya, H., Mita, K., Nishimoto, T., Sato, M. and Wada, Y
  • Journal Title: NeuroEndocrinol. Lett Volume: 33(1) Pages: 1-2
  • Peer Reviewed
• [Journal Article] GPR98/Gpr98 Gene Is Involved in the Regulation of Human and Mouse Bone Mineral Density (2012)
  • Author(s): Urano, T., Shiraki, M,. Yagi, H., Ito, M., Sasaki, N., Sato, M., Ouchi, Y. and Inoue, S
  • Journal Title: J . Clin. Endocrinol. Metab Volume: 97(4)
  • Peer Reviewed
• [Journal Article] A tightly controlled conditional knockdown system using the tol2 transposon-mediated technique (2012)
  • Author(s): Iguchi, T., Yagi, H., Wang, CC. and Sato, M
  • Journal Title: PLoS ONE Volume: 7(3)
  • Peer Reviewed
• [Journal Article] Maternal bisphenol A oral dosing relates to the acceleration of neurogenesis in the developing neocortex of mouse fetuses (2012)
  • Author(s): Komada, M., Asai, Y., Morii, M., Matsuki, M., Sato, M. and Nagao, T
  • Journal Title: Toxicology Volume: 16;295(1-3) Pages: 31-8
  • Peer Reviewed
• [Presentation] Phld2 regulates the maturation of dendritic spines and AMPA receptor endocytosis during long-term depression (2013)
  • Author(s): Xie, M.-J., Yagi, H., Iguchi, T., Oka, Y., Kuroda, K., Yuzaki, M., Matsuda, S., Shirao, T., Ishikawa, Y. and Sato, M
  • Organizer: Society For Neuroscience 2013
  • Place of Presentation: サンディエゴ
  • Year and Date: 2013-11-12
• [Presentation] Phldb2はAMPA受容体のエンドサイトーシスおよびLTDを制御する (2013)
  • Author(s): 謝敏カク
  • Organizer: 第14回ORIGIN神経科学研究会夏のワークショップ
  • Place of Presentation: 岐阜県下呂市
  • Year and Date: 2013-08-31
• [Presentation] Phldb2は樹状突起スパインの成熟および化学的LTD誘導後のシナプスでのAMPA受容体のエンドサイトーシスを制御する (2013)
  • Author(s): 謝敏カク,八木秀司,猪口徳一,岡雄一郎,黒田一樹,柚崎通介,松田信爾,白尾智明,石川保幸,佐藤真
  • Organizer: Neuro2013
  • Place of Presentation: 京都
  • Year and Date: 2013-06-21
• [Presentation] WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration (2012)
  • Author(s): Xie, M.-J., Yagi, H., Kuroda, K., Wang C.-C., Komada, M., Oka, Y., Iguchi, T. and Sato, M
  • Organizer: Neuroscience
  • Place of Presentation: Nagoya
  • Year and Date: 2012-09-21
• [Presentation] 皮質脊髄路の発達における軸策側枝形成因子の探索 (2012)
  • Author(s): 猪口徳一他
  • Organizer: 第117回日本解剖学会全国学術集会
  • Place of Presentation: 甲府市
• [Presentation] 神経細胞の棘状突起（スパイン）形成におけるFILIP関連分子の機能解析 (2012)
  • Author(s): 黒田一樹他
  • Organizer: 第117回日本解剖学会全国学術集会
  • Place of Presentation: 甲府市
• [Presentation] Dendritic growth cone activities are essential for completing multipolar-bipolar transition and starting glia-guided locomotion (2011)
  • Author(s): Xie, M-J., Yagi, H., Kuroda K., Wang C-C, Komada M., Iguchi, T. Sato, M
  • Organizer: Neuroscience
  • Place of Presentation: Washington
  • Year and Date: 2011-11-02
• [Presentation] 大脳皮質でのglia-guided locomotionの開始には、樹状突起の成長円錐が重要である (2011)
  • Author(s): 謝敏カク, 八木秀司, 黒田一樹, 駒田致和, 猪口徳一, 佐藤真
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-15
• [Presentation] Intermediate progenitorの増殖・分化におけるHedgehogシグナルの役割 (2011)
  • Author(s): 駒田 致和他
  • Organizer: 第51回日本先天異常学会学術集会
  • Place of Presentation: 東京
• [Presentation] 中間前駆細胞の増殖・分化におけるヘッジホッグシグナルの役割 (2011)
  • Author(s): 駒田致和他
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] 神経棘突起の形態調節におけるFILIPの役割 (2011)
  • Author(s): 八木秀司他
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Filip play a role in cortical development and spine morphology (2011)
  • Author(s): 八木秀司他
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 石川県山代
• [Presentation] Dendritic growth cone activities, regulated by Abl kinase and Cdk5 via WAVE2-Abi2, are essential for completing multipolar-bipolar transition and starting glia-guided locomotion. (2011)
  • Author(s): Xie, M.-J. et al.
  • Organizer: Society For Neuroscience 2011
  • Place of Presentation: ワシントン
• [Presentation] Phldb2は樹状突起スパインの成熟および化学的LTD誘導後のシナプスでのAMPA受容体のエンドサイトーシスを制御する。
  • Author(s): 謝 敏カク，八木秀司，猪口徳一，岡 雄一郎，黒田一樹，柚崎通介，松田信爾，白尾智明，石川保幸，佐藤 真
  • Organizer: Neuro2013
  • Place of Presentation: 京都、国立京都国際会館
• [Presentation] FILIP関連分子によるMyosin-IIbを介した神経細胞野ｽﾊﾟｲﾝ形成の制御とシナプス可塑性における機能解析。
  • Author(s): 黒田一樹，八木秀司，謝 敏カク，岡 雄一郎，猪口徳一，佐藤 真
  • Organizer: Neuro2013
  • Place of Presentation: 京都、国立京都国際会館
• [Presentation] Phldb2はAMPA受容体のエンドサイトーシスおよびLTDを制御する。
  • Author(s): 謝 敏カク
  • Organizer: 第14回ORIGIN神経科学研究会夏のワークショップ
  • Place of Presentation: 岐阜県下呂市、山形屋
• [Presentation] Phld2 regulates the maturation of dendritic spines and AMPA receptor endocytosis during long-term depression
  • Author(s): Xie, M.-J., Yagi, H., Iguchi, T., Oka, Y., Kuroda, K., Yuzaki, M., Matsuda, S., Shirao, T., Ishikawa, Y. and Sato, M
  • Organizer: Society For Neuroscience 2013
  • Place of Presentation: サンディエゴ、USA
• [Presentation] FILIP-related molecule controls spine maturation and synaptic function in the hippocampal neuron via non-muscle myosin IIb.
  • Author(s): Kuroda, K., Yagi, H., Xie, M.-J., Oka, Y., Iguchi, T. and Sato, M
  • Organizer: Society For Neuroscience 2013
  • Place of Presentation: サンディエゴ、USA
• [Presentation] Analyses on the potential candidates of collateral branch inducing factor that are specifically expressed in the targets of axon collaterals from the corticospinal projection
  • Author(s): Iguchi, T, et al.
  • Organizer: The 11th Biennial Meeting of the Asian-Pacific Society for Neurochemistry / 55th Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: 神戸
• [Presentation] FILIP-related molecule controls spine maturation in the hippcampal neuron via non-muscle myosin llb.
  • Author(s): Kuroda, K, et al.
  • Organizer: The 11th Biennial Meeting of the Asian-Pacific Society for Neurochemistry / 55th Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: 神戸
• [Presentation] A2-pancortins especially Pancortin-4, are involved in the neuronal cell desth after the ischemic stroke during the growth period.
  • Author(s): Wang, C.-C, et al.
  • Organizer: The 11th Biennial Meeting of the Asian-Pacific Society for Neurochemistry / 55th Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: 神戸
• [Presentation] FILIPによるアクチンミオシン調節能の棘突起動態変化への関与．
  • Author(s): 八木秀司他
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] WAVE-Abi2複合体はradial migration時の成長円錐の活性化およびmultipolar-bipolar transitionとglia-guided migrationの開始を制御する．
  • Author(s): 謝 敏カク他
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] Filip is involved in the morphological control of dendritic spine through actomyosin regulation
  • Author(s): Yagi, H et al.
  • Organizer: Society For Neuroscience 2012
  • Place of Presentation: ニューオリンズ （アメリカ）
• [Presentation] 神経細胞の棘突起（スパイン）形成におけるFILIP関連分子の機能解析．
  • Author(s): 黒田 一樹他
  • Organizer: 第118回日本解剖学会全国学術集会
  • Place of Presentation: 高松市
• [Remarks] 本研究の代表者(謝)は福井大学市民公開講座を担当し、講演を通じ情報を発信している(平成25年)