Deciphering mechanisms of synaptic remodeling at the morphological and functional levels

2009 Fiscal Year Final Research Report

• Project/Area Number: 17023010
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: BITO Haruhiko The University of Tokyo, 大学院・医学系研究科, 准教授 (00291964)
• Project Period (FY): 2005 – 2009
• Keywords: 脳・神経 / 神経科学 / シグナル伝達 / 蛋白質 / 生理学

Research Abstract

Through this program, we identified several new CREB-regulatory kinases. Furthermore, we showed that the immediate early gene Arc is a bona fide CREB target gene, and elucidated the transcriptional mechanisms implicated in activity-dependent Arc gene activation. Additionally, we characterized the essential roles of CaMKI isoforms in the growth of dendrites and axons during the perinatal development of neuronal circuits. Finally, novel modes of regulation of PSD and presynaptic active zone scaffolding proteins (such as PSD-95, RIM1 and Shank) were investigated, with emphasis on their link with actin cytoskeletal remodeling. In parallel, we developed new protocols to visualize and manipulate synapse formation and morphological remodeling of neurons.

Research Products

• [Journal Article] Synaptic tagging and capture: differential role of distinct calcium/calmodulin kinases in protein synthesis-dependent long-term potentiation. (2010)
  • Author(s): Redondo RL, Okuno H, Spooner PA, Frenguelli BG, Bito H, Morris RGM.
  • Journal Title: J. Neurosci. 30 Pages: 4981-4989
  • Peer Reviewed
• [Journal Article] Regulation of cortical axon growth by a GABA-driven Ca2+/calmodulin-dependent protein kinase cascade (2009)
  • Author(s): Ageta-Ishihara N, Takemoto-Kimura S, Nonaka M, Adachi-Morishima A, Suzuki K, Kamijo S, Fujii H, Mano T, Blaeser F, Chatila TA, Mizuno H, Hirano T, Tagawa Y, Okuno H, Bito H.
  • Journal Title: J. Neurosci. 29 Pages: 13720-13729
  • Peer Reviewed
• [Journal Article] A synaptic activity-responsive element in the Arc/Arg3. 1 promoter essential for synapse-to-nucleus signaling in activated neurons (2009)
  • Author(s): Kawashima T, Okuno H, Nonaka M, Adachi-Morishima A, Kyo N, Okamura M, Takemoto-Kimura S, Worley PF, Bito H.
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 316-321
  • Peer Reviewed
• [Journal Article] DCLK1 (2007)
  • Author(s): Fuse T, Ohmae S, Takemoto-Kimura S, Bito H.
  • Journal Title: AfCS/Nature Molecule Pages, doi:10. 1038 Pages: a003011.01
  • Peer Reviewed
• [Journal Article] The active zone protein RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels (2007)
  • Author(s): Kiyonaka S, Wakamori M, Miki T, Uriu Y, Nonaka M, Bito H, Beedle AM, Mori E, Hara Y, De Waard M, Kanagawa M, Itakura M, Takahashi M, Campbell KP, Mori Y.
  • Journal Title: Nature Neurosci 10 Pages: 691-701
  • Peer Reviewed
• [Journal Article] Regulation of dendritogenesis via a lipid raft-associated Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKIγ (2007)
  • Author(s): Takemoto-Kimura S, Ageta-Ishihara N, Nonaka M, Adachi-Morishima A, Mano T, Okamura M, Fujii H, Fuse T, Hoshino M, Suzuki S, M Kojima, Mishina M, Okuno H, Bito H.
  • Journal Title: Neuron 54 Pages: 755-770
  • Peer Reviewed
• [Journal Article] Regulation of osteoclast differentiation and function by the CaMK-CREB pathway. (2006)
  • Author(s): Sato K, Suematsu A, Nakashima T, Takemoto-Kimura S, Aoki K, Morishita Y, Asahara H, Ohya K, Yamaguchi A, Takai T, Kodama T, Chatila TA, Bito H, Takayanagi H.
  • Journal Title: Nature Med. 12 Pages: 1410-1416
  • Peer Reviewed
• [Journal Article] Differential control of postsynaptic density scaffolds via actin-dependent and independent mechanisms. (2006)
  • Author(s): Kuriu T, Inoue A, Bito H, Sobue K, Okabe S.
  • Journal Title: J. Neurosci. 26 Pages: 7693-7706
  • Peer Reviewed
• [Journal Article] Activity-dependent regulation of β-catenin via ε-cleavage of N-cadherin. (2006)
  • Author(s): Uemura K, Kihara T, Kuzuya A, Okawa K, Nishimoto T, Bito H, Ninomiya H, Sugimoto H, Kinoshita A, Shimohama S.
  • Journal Title: Biochem Biophys Res Commun. 345 Pages: 951-958
  • Peer Reviewed
• [Journal Article] Molecular identification and characterization of a family of kinases with homology to Ca2+/calmodulin-dependent protein kinases I/IV. (2006)
  • Author(s): Ohmae S, Takemoto-Kimura S, Okamura M, Adachi-Morishima A, Nonaka M, Fuse T, Kida S, Tanji M, Furuyashiki T, Arakawa Y, Narumiya S, Okuno H, Bito H.
  • Journal Title: J. Biol. Chem. 281 Pages: 20427-20439
  • Peer Reviewed
• [Journal Article] Essential contribution of the ligand-binding βB-βC loop of PDZ1 and PDZ2 in the regulation of postsynaptic clustering, scaffolding and localization of PSD-95 (2006)
  • Author(s): Nonaka M, Doi T, Fujiyoshi Y, Takemoto-Kimura S, Bito H.
  • Journal Title: J. Neurosci. 26 Pages: 763-774
  • Peer Reviewed
• [Journal Article] Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum (2005)
  • Author(s): Hoshino M, Nakamura S, Mori K, Kawauchi T, Terao M, Nishimura YV, Fukuda A, Fuse T, Matsuo N, Sone M, Watanabe M, Bito H, Terashima T, Wright CVE, Kawaguchi Y, Nakao K, Nabeshima Y.
  • Journal Title: Neuron 47 Pages: 201-213
  • Peer Reviewed
• [Journal Article] Prostaglandin E receptor EP1 controls impulsive behavior under stress. (2005)
  • Author(s): Matsuoka Y, Furuyashiki T, Yamada K, Nagai T, Bito H, Tanaka Y, Kitaoka S, Ushikubi F, Nabeshima T., Narumiya S.
  • Journal Title: Proc. Natl. Acad. Sci. USA 102 Pages: 16066-16071
  • Peer Reviewed
• [Journal Article] Ca2+ signaling coordinates the formation and the morphological maturation of neuronal circuits and synapses: an essential role for excitation-morphogenesis coupling via CaM kinases
  • Author(s): Takemoto-Kimura S, Suzuki K, Kamijo S, Ageta-Ishihara N, Fujii H, Okuno H, Bito H.
  • Journal Title: Eur. J. Neurosci. (in press)
  • Peer Reviewed
• [Journal Article] Widespread transcription at neuronal activity-regulated enhancers.
  • Author(s): Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME.
  • Journal Title: Nature (in press)
  • Peer Reviewed
• [Presentation] CaM kinase signaling in neuronal microdomains. (2010)
  • Author(s): Bito H.
  • Organizer: The 13th International Membrane Research Forum/ The 6th iCeMS International Symposium Featuring Nano-Meso Membrane Mechanisms
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20100127-20100129
• [Presentation] A pivotal role of a CaMKK-Ca2+/ calmodulin-dependent protein kinase I cascade in the radial migration of layer 2/3 cortical pyramidal neurons. Soc. Neurosci. Abstr. 409. 13, 2009. (2009)
  • Author(s): Takemoto-Kimura S, Adachi-Morishima A, Ageta-Ishihara N, Suzuki K, Nonaka M, Okamura M, Nishimura VY, Kawauchi T, Nakajima K, Okuno H, Bito H.
  • Organizer: 第39回北米神経科学学会年会
  • Place of Presentation: Chicago, USA. Poster.
  • Year and Date: 20091017-20091021
• [Presentation] Differential role of distinct calcium-calmodulin kinases in protein synthesis-dependent long-term potentiation Soc. Neurosci. Abstr. 235. 3, 2009. (2009)
  • Author(s): Redondo RL, Okuno H, Spooner PA, Frenguelli BG, Bito H, Morris RGM.
  • Organizer: 第39回北米神経科学学会年会
  • Place of Presentation: Chicago, USA. Poster.
  • Year and Date: 20091017-20091021
• [Presentation] Input-specific remodeling of postsynaptic density (PSD) proteins in Purkinje cell spines. Soc. Neurosci. Abstr. 697. 5, 2009. (2009)
  • Author(s): Fuse T, Bito H
  • Organizer: 第39回北米神経科学学会年会
  • Place of Presentation: Chicago, USA. Nanosymposium speaker.
  • Year and Date: 20091017-20090121
• [Presentation] A Critical genomic element for synaptic activity-dependent expression of Arc/Arg3. 1. J. Physiol. Sci. 59 Suppl. 1, 182. (2009)
  • Author(s): Okuno H, Kawashima T, Nonaka M, Kyo N, Bito H.
  • Organizer: 第36回国際生理学会世界大会(IUPS2009)
  • Place of Presentation: Kyoto, Japan. Poster
  • Year and Date: 20090727-20090801
• [Presentation] Synaptic Activity-dependent Regulation of Plasticity-related Gene Arc (2009)
  • Author(s): Bito H.
  • Organizer: The 4th International conference of Neurons and Brain Diseases
  • Place of Presentation: Toronto, Canada.
  • Year and Date: 20090721-20090723
• [Presentation] Protein synthesis-dependent synaptic potentiation: a multidisciplinary analysis of the 'synaptic tagging and capture' theory (2009)
  • Author(s): Morris RGM, Bito H, Bonhoeffer T, Van Rossum M.
  • Organizer: Ninth HFSP Awardees Meeting and 20th Anniversary Celebration.
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20090601-20090604
• [Presentation] Distinct regulation of cortical axonal and dendritic development by two Ca2+-CaMKI pathways. Soc. Neurosci. Abstr. 606. 4 (2008)
  • Author(s): Ageta-Ishihara, N., Takemoto-Kimura, S., Adachi-Morishima, A., Nonaka, M., Okuno, H., Bito H.
  • Organizer: 第38回北米神経科学学会年会
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20081115-20081119
• [Presentation] Critical genomic sequences for synaptic activity-dependent expression of the Arc gene. Soc. Neurosci. Abstr. 38. 12 (2008)
  • Author(s): Okuno, H., Kawashima, T., Adachi-Morishima, A., Okamura, M., Worley, P., Bito, H.
  • Organizer: 第38回北米神経科学学会年会
  • Place of Presentation: Washington DC, USA. Poster.
  • Year and Date: 20081115-20081119
• [Presentation] Regulation of excitation-morphogenesis coupling by CaMKK/CaMKI cascades. (2008)
  • Author(s): Bito H.
  • Organizer: The 3rd International Conference on Neurons and Brain Diseases
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20080805-20080807
• [Presentation] Regulation of synaptic localization of Arc protein through interaction with Ca2+/calmodulin-dependent kinase II beta (2008)
  • Author(s): Okuno H., Kawashima T, Nonaka M., Takemoto-Kimura S, Fujii H., Chowdhury S., Worley P.F., Bito H.
  • Organizer: 6th FENS Forum 2008
  • Place of Presentation: Geneva, Switzerland, Poster.
  • Year and Date: 20080712-20080716
• [Presentation] Imaging of biochemical signaling at single synapse resolution (2008)
  • Author(s): Bito, H., Fujii, H., Takemoto-Kimura, S., Okuno, H.
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
  • Year and Date: 20080709-20080711
• [Presentation] Elucidating the critical role of CaMKK/CaMKI pathways in neuronal morphogenesis脳研究シナプス発達と神経伝達物質受容体トラフィッキングに関するワークショップ (2008)
  • Author(s): Bito H.
  • Organizer: US-Japan Brain Research Collaborative Program "Workshop on Receptor Trafficking and Cell Biology of Neurons: Physiology and Disease"
  • Place of Presentation: Asilomar Conference Center, Pacific Grove, California, USA.
  • Year and Date: 20080224-20080227
• [Presentation] New functions for CaM kinases in neurite growth (2008)
  • Author(s): 上田(石原)奈津実、竹本-木村さやか、野中美応、安達-森島亜希、奥野浩行、尾藤晴彦
  • Organizer: 第60回日本細胞生物学会ミニシンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-29
• [Presentation] The active zone protein RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels. Soc. Neurosci. Abstr. 853. 5. (2007)
  • Author(s): Kiyonaka S, Wakamori M, Miki T, Uriu Y, Nonaka M, Bito H, Beedle AM, Mori E, Hara Y, De Waard M, Kanagawa M, Itakura M, Takahashi M, Campbell KP, Mori Y.
  • Organizer: 第37回北米神経科学学会年会
  • Place of Presentation: San Diego, USA. Oral.
  • Year and Date: 20071103-20071107
• [Presentation] Neonatal isolation induces susceptibility to learned helplessness through the decrease in LIMK1 in the adult rat hippocampus. Soc. Neurosci. Abstr. 501. 2. (2007)
  • Author(s): Morinobu S, Takahashi T, Iwamoto Y, Kawano K-I, Yamawaki S, Okuno H, Bito H.
  • Organizer: 第37回北米神経科学学会年会
  • Place of Presentation: San Diego, USA. poster
  • Year and Date: 20071103-20071107
• [Presentation] Requirement for palmitoylation and raft insertion of Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKIγduring cortical dendritogenesis. Soc. Neurosci. Abstr. 240. 13. (2007)
  • Author(s): Takemoto-Kimura S, Ageta-Ishihara N, Nonaka M, Okuno H, Bito H.
  • Organizer: 第37回北米神経科学学会年会
  • Place of Presentation: San Diego, USA. poster
  • Year and Date: 20071103-20071107
• [Presentation] Synaptic targeting of Arc via high affinity interaction with Ca2+/calmodulin-dependent kinase II beta. Soc. Neurosci. Abstr. 221. 3. (2007)
  • Author(s): Okuno H, Naruse H, Kawashima T, Fujii H, Nonaka M, Chowdhury S., Worley P, Bito H.
  • Organizer: 第37回北米神経科学学会年会
  • Place of Presentation: San Diego, USA. Oral.
  • Year and Date: 20071103-20071107
• [Presentation] Differential control of cortical axonogenesis and dendritogenesis by alternate activation of CaMKIαandγ. Soc. Neurosci. Abstr. 114. 3, 2007. (2007)
  • Author(s): Ageta-Ishihara N, Takemoto-Kimura S, Nonaka M, Fujii H, Okuno H, Bito H.
  • Organizer: 第37回北米神経科学学会年会
  • Place of Presentation: San Diego, USA. Oral.
  • Year and Date: 20071103-20071107
• [Presentation] Actin-dependent regulation of Shank dynamics in Purkinje cell dendrites. Soc. Neurosci. Abstr. 45. 8, 2007. (2007)
  • Author(s): Fuse T, Bito H.
  • Organizer: 第37回北米神経科学学会年会
  • Place of Presentation: San Diego, USA. poster
  • Year and Date: 20071103-20071107
• [Presentation] Molecular biology and neuronal functions of CaMK family genes. (2007)
  • Author(s): Takemoto-Kimura S, Ageta-Ishihara N, Fujii H, Okamura M, Okuno H, Bito H.
  • Organizer: International Symposium on Advanced Functional Genomics.
  • Place of Presentation: Kazusa, Chiba, Japan
  • Year and Date: 20071011-20071012
• [Presentation] Optical analysis of activity-dependent protein synthesis in dendritic regions of neurons (2007)
  • Author(s): Okuno H, Naruse H, Bito H.
  • Organizer: 2nd International workshop on Approaches to Single-Cell Analysis
  • Place of Presentation: Tokyo, Japan. Poster
  • Year and Date: 20070906-20070907
• [Presentation] Regulation of dendritogenesis via a lipid raft-associated Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKIγ2nd (2007)
  • Author(s): Takemoto-Kimura S, Ageta-Ishihara N, Nonaka M, Okuno H, Bito H.
  • Organizer: International Conference of Neurons and Brain Disease
  • Place of Presentation: Toronto, Canada
  • Year and Date: 20070829-20070831
• [Book] in "Molecular Pain"(M. Zhuo ed., Activity-dependent gene regulation: How do synapses talk to the nucleus and fine-tune neuronal outputs?) (2008)
  • Author(s): Bito H, Takemoto-Kimura S, Okuno H.
  • Publisher: Springer
• [Book] 情報素子としてのシナプス-構造・機能ならびに新たな疾患制御標的としての意義-(宇理須恒雄 編, inナノメディシン) (2008)
  • Author(s): 奥野浩行、藤井哉、尾藤晴彦
  • Total Pages: 220-233
  • Publisher: オーム社
• [Book] 神経細胞内ではたらくシグナル伝達(甘利 俊一 監修, 古市 貞一 編, Inシリーズ脳科学第5巻分子・細胞・シナプスからみる脳) (2008)
  • Author(s): 尾藤晴彦、有賀純
  • Total Pages: 131-180