Updated on 2021/04/04

写真a

 
TAKEMOTO-KIMURA Sayaka MD PhD
 
Organization
Nagoya University Research Institute of Environmental Medicine Division of Stress Recognition and Response Professor
Title
Professor
Contact information
メールアドレス

Degree 1

  1. 博士(医学) ( 2003.9   京都大学 ) 

Research Areas 2

  1. Others / Others  / 分子神経科学

  2. Others / Others  / Molecular Neuroscience

Research History 4

  1. Professor, Research institute of Environmental Medicine, Nagoya University

    2015.7

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    Country:Japan

  2. Assistant Professor, Department of Neurochemistry, The University of Tokyo Graduate School of Medicine

    2014.4 - 2015.6

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    Country:Japan

  3. Junior Assistant Professor, Department of Neurochemistry, The University of Tokyo Graduate School of Medicine

    2003.10 - 2014.3

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    Country:Japan

  4. Resident, Nagoya University Hospital

    1999.6 - 2000.3

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    Country:Japan

Education 2

  1. Kyoto University   Graduate School, Division of Medicine

    - 2003

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    Country: Japan

  2. Nagoya University   Faculty of Medicine

    - 1999

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    Country: Japan

Awards 1

  1. 日本神経化学会奨励賞

    2012   日本神経化学会  

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    Country:Japan

 

Papers 26

  1. A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development

    Horigane Shin-ichiro, Ozawa Yukihiro, Zhang Jun, Todoroki Hiroe, Miao Pan, Haijima Asahi, Yanagawa Yuchio, Ueda Shuhei, Nakamura Shigeo, Kakeyama Masaki, Takemoto-Kimura Sayaka

    FEBS OPEN BIO   Vol. 10 ( 8 ) page: 1436 - 1446   2020.8

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/2211-5463.12924

    Web of Science

  2. Calcium signalling: a key regulator of neuronal migration

    Horigane Shin-ichiro, Ozawa Yukihiro, Yamada Hirokazu, Takemoto-Kimura Sayaka

    JOURNAL OF BIOCHEMISTRY   Vol. 165 ( 5 ) page: 401 - 409   2019.5

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/jb/mvz012

    Web of Science

  3. Retained Plasticity and Substantial Recovery of Rod-Mediated Visual Acuity at the Visual Cortex in Blind Adult Mice with Retinal Dystrophy

    Nishiguchi Koji M, Fujita Kosuke, Tokashiki Naoyuki, Komamura Hiroshi, Takemoto-Kimura Sayaka, Okuno Hiroyuki, Bito Haruhiko, Nakazawa Toru

    MOLECULAR THERAPY   Vol. 26 ( 10 ) page: 2397 - 2406   2018.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.ymthe.2018.07.012

    Web of Science

  4. A Critical Neurodevelopmental Role for L-Type Voltage-Gated Calcium Channels in Neurite Extension and Radial Migration. International journal

    Satoshi Kamijo, Yuichiro Ishii, Shin-Ichiro Horigane, Kanzo Suzuki, Masamichi Ohkura, Junichi Nakai, Hajime Fujii, Sayaka Takemoto-Kimura, Haruhiko Bito

    The Journal of neuroscience : the official journal of the Society for Neuroscience   Vol. 38 ( 24 ) page: 5551 - 5566   2018.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    Despite many association studies linking gene polymorphisms and mutations of L-type voltage-gated Ca2+ channels (VGCCs) in neurodevelopmental disorders such as autism and schizophrenia, the roles of specific L-type VGCC during brain development remain unclear. Calcium signaling has been shown to be essential for neurodevelopmental processes such as sculpting of neurites, functional wiring, and fine tuning of growing networks. To investigate this relationship, we performed submembraneous calcium imaging using a membrane-tethered genetically encoded calcium indicator (GECI) Lck-G-CaMP7. We successfully recorded spontaneous regenerative calcium transients (SRCaTs) in developing mouse excitatory cortical neurons prepared from both sexes before synapse formation. SRCaTs originated locally in immature neurites independently of somatic calcium rises and were significantly more elevated in the axons than in dendrites. SRCaTs were not blocked by tetrodoxin, a Na+ channel blocker, but were strongly inhibited by hyperpolarization, suggesting a voltage-dependent source. Pharmacological and genetic manipulations revealed the critical importance of the Cav1.2 (CACNA1C) pore-forming subunit of L-type VGCCs, which were indeed expressed in immature mouse brains. Consistently, knocking out Cav1.2 resulted in significant alterations of neurite outgrowth. Furthermore, expression of a gain-of-function Cav1.2 mutant found in Timothy syndrome, an autosomal dominant multisystem disorder exhibiting syndromic autism, resulted in impaired radial migration of layer 2/3 excitatory neurons, whereas postnatal abrogation of Cav1.2 enhancement could rescue cortical malformation. Together, these lines of evidence suggest a critical role for spontaneous opening of L-type VGCCs in neural development and corticogenesis and indicate that L-type VGCCs might constitute a perinatal therapeutic target for neuropsychiatric calciochannelopathies.SIGNIFICANCE STATEMENT Despite many association studies linking gene polymorphisms and mutations of L-type voltage-gated Ca2+ channels (VGCCs) in neurodevelopmental disorders such as autism and schizophrenia, the roles of specific L-type VGCCs during brain development remain unclear. We here combined the latest Ca2+ indicator technology, quantitative pharmacology, and in utero electroporation and found a hitherto unsuspected role for L-type VGCCs in determining the Ca2+ signaling landscape of mouse immature neurons. We found that malfunctional L-type VGCCs in immature neurons before birth might cause errors in neuritic growth and cortical migration. Interestingly, the retarded corticogenesis phenotype was rescued by postnatal correction of L-type VGCC signal aberration. These findings suggest that L-type VGCCs might constitute a perinatal therapeutic target for neurodevelopment-associated psychiatric disorders.

    DOI: 10.1523/JNEUROSCI.2357-17.2018

    Web of Science

    PubMed

  5. Calmodulin kinases: essential regulators in health and disease Reviewed

    Sayaka Takemoto-Kimura, Kanzo Suzuki, Shin-Ichiro Horigane, Satoshi Kamijo, Masatoshi Inoue, Masayuki Sakamoto, Hajime Fujii, Haruhiko Bito

    JOURNAL OF NEUROCHEMISTRY   Vol. 141 ( 6 ) page: 808 - 818   2017.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    Neuronal activity induces intracellular Ca2+ increase, which triggers activation of a series of Ca2+-dependent signaling cascades. Among these, the multifunctional Ca2+/calmodulin-dependent protein kinases (CaMKs, or calmodulin kinases) play key roles in neuronal transmission, synaptic plasticity, circuit development and cognition. The most investigated CaMKs for these roles in neuronal functions are CaMKI, CaMKII, CaMKIV andwe will shed light on these neuronal CaMKs' functions in this review. Catalytically active members of CaMKs currently are CaMKI, CaMKII, CaMKIV and CaMKK. Although they all necessitate the binding of Ca2+ and calmodulin complex (Ca2+/CaM) for releasing autoinhibition, each member of CaMK has distinct activation mechanisms-autophosphorylation mediated autonomy of multimeric CaMKII and CaMKK-dependent phosphoswitch-induced activation of CaMKI or CaMKIV. Furthermore, each CaMK shows distinct subcellular localization that underlies specific compartmentalized function in each activated neuron. In this review, we first summarize these molecular characteristics of each CaMK as to regulation and subcellular localization, and then describe each biological function. In the last section, we also focus on the emerging role of CaMKs in pathophysiological conditions by introducing the recent studies, especially focusing on drug addiction and depression, and discuss how dysfunctional CaMKs may contribute to the pathology of the neuropsychological disorders.

    DOI: 10.1111/jnc.14020

    Web of Science

  6. Exploring the function of calcium-dependent phosphorylation in neuronal morphogenesis and circuit formation. Invited

    Takemoto-Kimura S and Horigane S

    Jpn. J. Neuropsychopharmaol.     page: 163-167   2017

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 163-167

  7. Facilitation of axon outgrowth via a Wnt5a-CaMKK-CaMKIα pathway during neuronal polarization

    Horigane S*, Ageta-Ishihara N*, Kamijo S, Fujii H, Okamura M, Kinoshita M, Takemoto-Kimura S**, Bito H** (*co-first; **co-corresponding authors)

        2016.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1186/s13041-016-0189-3

  8. Rational design of a high-affinity, fast, red calcium indicator R-CaMP2.

    Inoue M, Takeuchi A, Horigane S, Ohkura M, Gengyo-Ando K, Fujii H, Kamijo S, Takemoto-Kimura S, Kano M, Nakai J, Kitamura K, Bito H

    Nature methods   Vol. 12 ( 1 ) page: 64-70   2015.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nmeth.3185

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  9. Towards a better understanding of cognitive behaviors regulated by gene expression downstream of activity-dependent transcription factors.

    Nonaka M, Kim R, Sharry S, Matsushima A, Takemoto-Kimura S, Bito H

    Neurobiology of learning and memory   Vol. 115   page: 21-9   2014.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.nlm.2014.08.010

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  10. Region-specific activation of CRTC1-CREB signaling mediates long-term fear memory.

    Nonaka M, Kim R, Fukushima H, Sasaki K, Suzuki K, Okamura M, Ishii Y, Kawashima T, Kamijo S, Takemoto-Kimura S, Okuno H, Kida S, Bito H

    Neuron   Vol. 84 ( 1 ) page: 92-106   2014.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.neuron.2014.08.049

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  11. Functional labeling of neurons and their projections using the synthetic activity-dependent promoter E-SARE.

    Kawashima T, Kitamura K, Suzuki K, Nonaka M, Kamijo S, Takemoto-Kimura S, Kano M, Okuno H, Ohki K, Bito H

    Nature methods   Vol. 10 ( 9 ) page: 889-95   2013.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nmeth.2559

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  12. Nonlinear decoding and asymmetric representation of neuronal input information by CaMKIIα and calcineurin.

      Vol. 3 ( 4 ) page: 978-87   2013.4

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.celrep.2013.03.033

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  13. Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ.

      Vol. 149 ( 4 ) page: 886-98   2012.5

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    DOI: 10.1016/j.cell.2012.02.062

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  14. Differential roles for CaM kinases in mediating excitation-morphogenesis coupling during formation and maturation of neuronal circuits.

    Takemoto-Kimura S, Suzuki K, Kamijo S, Ageta-Ishihara N, Fujii H, Okuno H, Bito H

    The European journal of neuroscience   Vol. 32 ( 2 ) page: 224-30   2010.7

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    DOI: 10.1111/j.1460-9568.2010.07353.x

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  15. Control of cortical axon elongation by a GABA-driven Ca2+/calmodulin-dependent protein kinase cascade.

    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

    The Journal of neuroscience : the official journal of the Society for Neuroscience   Vol. 29 ( 43 ) page: 13720-9   2009.10

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    DOI: 10.1523/JNEUROSCI.3018-09.2009

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  16. Synaptic activity-responsive element in the Arc/Arg3.1 promoter essential for synapse-to-nucleus signaling in activated neurons.

    Kawashima T, Okuno H, Nonaka M, Adachi-Morishima A, Kyo N, Okamura M, Takemoto-Kimura S, Worley PF, Bito H

    Proceedings of the National Academy of Sciences of the United States of America   Vol. 106 ( 1 ) page: 316-21   2009.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1073/pnas.0806518106

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  17. [Molecular mechanisms underlying the regulation of synapse function and the molecular architecture of the postsynaptic density].

    Bito H, Nonaka M, Fuse T, Fujii H, Takemoto-Kimura S, Okuno H

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   Vol. 53 ( 4 Suppl ) page: 418-23   2008.3

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

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  18. Regulation of dendritogenesis via a lipid-raft-associated Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKIgamma.

    Takemoto-Kimura S, Ageta-Ishihara N, Nonaka M, Adachi-Morishima A, Mano T, Okamura M, Fujii H, Fuse T, Hoshino M, Suzuki S, Kojima M, Mishina M, Okuno H, Bito H

    Neuron   Vol. 54 ( 5 ) page: 755-70   2007.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.neuron.2007.05.021

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  19. Regulation of osteoclast differentiation and function by the CaMK-CREB pathway.

    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

    Nature medicine   Vol. 12 ( 12 ) page: 1410-6   2006.12

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nm1515

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  20. Molecular identification and characterization of a family of kinases with homology to Ca2+/calmodulin-dependent protein kinases I/IV.

    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

    The Journal of biological chemistry   Vol. 281 ( 29 ) page: 20427-39   2006.7

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    DOI: 10.1074/jbc.M513212200

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  21. Essential contribution of the ligand-binding beta B/beta C loop of PDZ1 and PDZ2 in the regulation of postsynaptic clustering, scaffolding, and localization of postsynaptic density-95.

    Nonaka M, Doi T, Fujiyoshi Y, Takemoto-Kimura S, Bito H

    The Journal of neuroscience : the official journal of the Society for Neuroscience   Vol. 26 ( 3 ) page: 763-74   2006.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1523/JNEUROSCI.2489-05.2006

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  22. [Synaptic activity-dependent regulation of neuronal gene expression].

    Okuno H, Takemoto-Kimura S, Ohmae S, Okamura M, Ishihara N, Bito H

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   Vol. 49 ( 3 Suppl ) page: 411-8   2004.2

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

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  23. Ca(2+)/CREB/CBP-dependent gene regulation: a shared mechanism critical in long-term synaptic plasticity and neuronal survival.

    Bito H, Takemoto-Kimura S

    Cell calcium   Vol. 34 ( 4-5 ) page: 425-30   2003.10

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  24. Molecular cloning and characterization of CLICK-III/CaMKIgamma, a novel membrane-anchored neuronal Ca2+/calmodulin-dependent protein kinase (CaMK).

    Takemoto-Kimura S, Terai H, Takamoto M, Ohmae S, Kikumura S, Segi E, Arakawa Y, Furuyashiki T, Narumiya S, Bito H

    The Journal of biological chemistry   Vol. 278 ( 20 ) page: 18597-605   2003.5

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    DOI: 10.1074/jbc.M300578200

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  25. Control of axon elongation via an SDF-1alpha/Rho/mDia pathway in cultured cerebellar granule neurons.

    Arakawa Y, Bito H, Furuyashiki T, Tsuji T, Takemoto-Kimura S, Kimura K, Nozaki K, Hashimoto N, Narumiya S

    The Journal of cell biology   Vol. 161 ( 2 ) page: 381-91   2003.4

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    DOI: 10.1083/jcb.200210149

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  26. Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltage-gated Ca2+ channels.

    Furuyashiki T, Arakawa Y, Takemoto-Kimura S, Bito H, Narumiya S

    Proceedings of the National Academy of Sciences of the United States of America   Vol. 99 ( 22 ) page: 14458-63   2002.10

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    DOI: 10.1073/pnas.212148999

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Research Project for Joint Research, Competitive Funding, etc. 3

  1. カルシウムシグナル破綻に基づく精神疾患の分子細胞基盤解明と新規介入戦略の樹立

    2016.5

    脳科学研究戦略推進プログラム(脳プロ)  

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    Grant type:Competitive

  2. 脳深部微小神経回路を構成する細胞個性の機能的・分子的解読と情動制御への応用

    2015.10 - 2019.3

    戦略的創造研究推進事業(さきがけ) 

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    Grant type:Competitive

  3. リン酸化による大脳辺縁系情動回路修飾機構の解明

    2010.10 - 2014.3

    戦略的創造研究推進事業(さきがけ) 

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    Grant type:Competitive

KAKENHI (Grants-in-Aid for Scientific Research) 7

  1. 神経細胞移動を制御するカルシウム依存的分子細胞機構の解明

    2016.4

    科学研究費補助金  基盤研究(B)

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    Authorship:Principal investigator 

  2. 分界条床核特定神経回路を介した不安生起機構

    2015.4 - 2017.3

    科学研究費補助金 

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    Authorship:Principal investigator 

  3. 神経回路形成を制御する新規カルシウム依存的リン酸化シグナリング機構の解明

    2011.4 - 2015.3

    科学研究費補助金  若手研究(A)

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    Authorship:Principal investigator 

  4. 脂質修飾型CaMキナーゼによる神経機能制御

    2008 - 2009

    科学研究費補助金  若手研究(B)

  5. アクチン動態を制御するCaMKK-CaMKIカスケードの神経機能解明

    2008 - 2009

    科学研究費補助金  若手研究(B)

  6. 蛋白質脂質修飾による膜挿入型CaMキナーゼCLICK-IIIの機能制御

    2006 - 2007

    科学研究費補助金  若手研究(B)

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    脳機能を担う神経回路の形成は、もともと球状である神経細胞が、細胞の骨組みである細胞骨格を利用して形を変化させ、樹状突起軸索と呼ばれる突起を発達させることで完成する。
    本研究課題では、CaMキナーゼCLICK-IIIの神経回路形成における機能を神経細胞培養のモデル系を用いて探索し、さらに本酵素の受ける蛋白質脂質修飾によって酵素機能がどのように修飾を受けるのか解明することを目的とした。
    まず、ラット大脳皮質神経細胞の樹状突起形成・伸展を培養下で観察する方法を確立した。本培養神経細胞において、RNAi法やノックアウトマウスを用いてCLICK-IIIの発現量を減少させると樹状突起形成が阻害され、逆に発現ベクターを用いて同発現を増加させると樹状突起形成が促進された。更に、本作用は神経栄養因子であるBDNFの効果発現においても寄与していることを明らかとした。分子レベルでは、CLICK-IIIが脂質と共有結合しラフト膜上に存在する結果、アクチン制御蛋白質Racを活性化することが、樹状突起形成作用の引き金となることを突き止め、樹状突起形成における蛋白質脂質修飾の重要性を分子レベルではじめて立証した。これらの成果は新たな樹状突起形成制御機構として注目され、Neuron誌にて掲載された。

  7. 新規膜挿入型CaMキナーゼCLICK-III/CaMKIγの神経機能解析

    2004 - 2005

    科学研究費補助金  若手研究(B)

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    本研究は、CaMKIファミリーに属する神経細胞特異的なCaMキナーゼ、CLICK-III/CaMKIγの、神経機能解明ならびにその分子機構の理解を目的とする。
    研究代表者は、前年度に本酵素がプレニル化ならびにパルミトイル化という複数の脂質修飾を受け膜アンカーされることを見出していたため、平成17年度は引き続き脂質修飾の制御ならびに生物学的意義についての研究を進めた。
    まず、2種類の脂質修飾であるプレニル化とパルミトイル化が互いに影響するか、各脂質修飾欠失変異体を用いて検討した。その結果、パルミトイル化を受けるためにはプレニル化を必要とする一方、パルミトイル化の有無によりプレニル化は影響されないことが分かり、細胞内において本酵素は、プレニル化、パルミトイル化を順序立って受けていることが示唆された。また、近年同定されたパルミトイル化酵素のうち、CLICK-IIIを基質とする候補分子を同定した。
    次に、CLICK-IIIの細胞生物学的機能について神経突起伸展のモデル細胞であるPC-12細胞を用いて検討した。CLICK-IIIを発現しないPC-12細胞にCLICK-IIIを発現させると、脱分極刺激によって誘導される突起伸展を促進することが分かった。更にこの作用は、脂質修飾欠失変異体においては減弱しており、脂質修飾が機能発現において重要な役割を果たすことが示唆された。
    以上の研究成果は...

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