1. 横浜市立大学大学院・医学研究科 生理学












     

     

     

    大学院医学研究科

     

     


     


    教室員の紹介

    竹本 研 (たけもと きわむ)


    (研究テーマ)
    1.神経伝達物質受容体の光不活化技術の開発

     CALI法は、標的分子を光で酸化・不活性化する分子操作技術のひとつであり、直径数マイクロメーターの微小領域においても迅速な分子不活化が可能です。この高い時間・空間分解能を生かして、シナプス表面で機能する神経伝達物質受容体を脳領域〜単一シナプスレベルで光不活化できれば記憶情報の詳細かつ因果的な解析が可能です。本研究ではエオシンCALI法(Takemoto K. et  al. ACS. Chem. Biol. 2011)と抗体工学を駆使し、神経伝達物質受容体を光で不活化する新技術の開発とその応用を進めています(Takemoto K. et al. Nat. Biotechnol. 2017)。

    2. 新しいCALI法の開発
     抗体を用いるCALI法では、分子ごとにCALIが可能な抗体を取得する必要があるため、様々な分子に対して網羅的に適用することは困難です。本研究では、進化分子工学的手法やタンパク質工学的手法を駆使し、様々な内在性分子をハイスループットかつゲノムワイドに光不活性化可能な、新規光学技術の創生を目指しています。

    3. CALI法を応用した医療技術の開発
     これまで培ったCALI法に関する技術基盤を元に、がん細胞や疾患原因物質を光で迅速に不活性化する新技術の開発を進めています。



    (全業績リスト)
    20.Trusel M, Nuno-Perez A, Lecca S, Harada H, Lalive A, Congiu M, Takemoto K, Takahashi T, Ferraguti F, Mameli M
    "Punishment-predictive cues guide avoidance through potentiation of hypothalamus-to-habenula synapses"
    Neuron in press

    19. Riani YD, Matsuda T, Takemoto K and Nagai T
    "Green monomeric photosensitizing fluorescent protein for photo-inducible protein inactivation and cell ablation."
    BMC Biol. 16(1):50, 2018

    18. Tada H, Miyazaki T, Takemoto K , Jitsuki S, Nakajima W, Koide M, Yamamoto N, Taguchi A, Kawai H, Komiya K, Suyama K, Abe H, Sano A and Takahashi T
    "Social isolation suppresses actin dynamics and synaptic plasticity through ADF/cofilin inactivation in the developing rat barrel cortex."
    Sci. Rep., 8471, 2017

    17. Takemoto K*(co-corresponding author), Iwanari H, Tada H, Suyama K, Sano A, Nagai T, Hamakubo T and Takahashi T*
    "Optical inactivation of synaptic AMPA receptors erases fear memory"
    Nat. Biotechnol., 35(1);38-47, 2017
    See also NEWS AND VIEWS

    16. Tada H, Miyazaki T, Takemoto K, Takase K, Jitsuki S, Nakajima W, Koide M, Yamamoto N, Komiya K, Suyama K, Sano A, Taguchi A and Takahashi T
    "Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex"
    Proc Natl Acad Sci U S A.,1606351113, 2016

    15. Sakamaki K, Ishii MT, Sakata T, Takemoto K, Takagi C, Takeuchi A, Morishita R, Takahashi H, Nozawa A, Shinoda H, Chiba K, Sugimoto H, Saito A, Tamate S, Satou Y, Sang-Kee J, Matsuoka S, Koyamada K, Sawasaki T, Nagai T and Ueno N
    "Dysregulation of a potassium channel, THIK-1, targeted by caspase-8 accelerates cell shrinkage"
    Biochem.Biophys.Acta., 1863(11);2766-2783, 2016

    14. Jitsuki S, Nakajima W, Takemoto K , Sano A, Tada H, Takahashi-Jitsuki A, Takahashi T.
    "Nogo Receptor Signaling Restricts Adult Neural Plasticity by Limiting Synaptic AMPA Receptor Delivery"
    Cerebral Cortex, 26(1); 427-439, 2016

    13. Liu T, Yamaguchi Y, Shirasaki Y, Shikada K, Hoshino K, Kaisho T, Takemoto K , Suzuki T, Kuranaga E, Ohara O, Miura M.
    "Single-cell
    imaging of caspase-1 dynamics reveals an all-or none inflammasome signaling responce"
    Cell Rep.
    8(4):974-982, 2014.

    12. Yamaguchi Y, Kuranaga E, Nakajima Y, Koto A, Takemoto K, Miura M.
    "In vivo monitoring of caspase activation using a fluorescence resonance energy transfer-based fluorescent probe"
    Methods Enzymol., 544; 299-325, 2014
    .

    11. Takemoto K , Matsuda T, Sakai N, Fu D, Noda M, Uchiyama S, Kotera I, Arai Y, Horiuchi M, Fukui K, Ayabe T, Inagaki F, Suzuki H, Nagai T.
    "SuperNova, a monomeric photosensitizing fluorescent protein for chromophore-assisted light inactivation"
    Sci. Rep., 3; 2629, 2013.

    10. Ohtsuka K, Sato S, Sato Y, Sota K, Ohzawa S, Matsuda T, Takemoto K, Takamune N, Juskowiak B, Nagai T, Takenaka S
    "Fluorescence imaging of potassium ions in living cells using a fluorescent probe based a thrombin binding aptamer-peptide conjyugate"
    Chem. Commun. 48(39):4740-2, 2012.

    9. Yamaguchi Y, Shinotsuka N, Nonomura K, Takemoto K , Kuida K, Yoshida H, Miura M.
    “Live imaging of apoptosis in a novel transgenic mouse highlights its role in neural tube closure“
    J.Cell.Biol. 195(6): 1047-60, 2011.

    8. Takemoto K , Matsuda T, McDougall M, Klaubert DH, Hasegawa A, Los GV, Wood KV, Miyawaki A, Nagai T.
    “Chromophore-assisted light inactivation of HaloTag fusion proteins labeled with eosin in living cells“
    ACS Chem Biol. 6(5): 401-6, 2011.

    7. Kuranaga E, Matsunuma T, Kanuka H, Takemoto K , Koto A, Kimura K, Miura M.
    "Apotosis controls the speed of looping morphogenesis in Drosophila male terminalia"
    Development. 138(8): 1493-9, 2011.

    6. Jitsuki S, Takemoto K , Kawasaki T, Tada H, Takahashi A, Becamel C, Sano A, Yuzaki M, Zukin RS, Ziff EB, Kessels HW, and Takahashi T.
    "Serotonin mediates cross-modal reorganization of cortical circuits".
    Neuron, 69, 780-792, 2011.

    5. Takemoto K , Kuranaga E, Tonoki A, Nagai T, Miyawaki A and Miura M.
    “Local initiation of caspase activation in Drosophila salivary gland programmed cell death in vivo “
    Proc Natl Acad Sci U S A. 104(33): 13367-13372, 2007. 

    4. Kuranaga E, Kanuka H, Tonoki A, Takemoto K , Tomioka T, Kobayashi M, Hayashi S and Miura M.
    “Drosophila IKK-Related Kinase regulates non-apoptotic function of caspases via degradation of IAPs”
    Cell 126(3): 583-596, 2006.

    3. Kanuka H., Kuranaga E., Takemoto K ., Hiratou T., Okano H., and Miura M.
    “Drosophila caspase transduces Shaggy/GSK-3b kinase activity in neural precuorsor development.”
    EMBO J. 24(21): 3793-3806, 2005.

    2. Takemoto K , Nagai T, Miyawaki A, and Miura M.
    “Spatio-temporal activation of caspase revealed by indicator that is insensitive to environmental effects”
    J.Cell Biol. 160(2): 235-243, 2003.
    See also
    In This Issue.

    1. Uetsuki T, Takemoto K , Nishimura I, Okamoto M, Niinobe M, Momoi T, Miura M and Yoshikawa K.
    “Activation of Neuronal Caspase-3 by Intracellular Accumulation of Wild-Type Alzheimer Amyloid Precursor Protein”
    J.Neurosci. 19(16): 6955-6964, 1999.