小西 慶幸

所属部署名生物応用化学講座
教員組織生物応用化学講座
教育研究組織工学部・工学研究科
職名教授
更新日: 19/07/23 19:11

研究者基本情報

氏名

    小西 慶幸
    コニシ ヨシユキ
    KONISHI Yoshiyuki

所属

  •  生物応用化学講座 教授

学歴

  • 1997年04月- 2000年03月千葉大学
  • 1995年04月- 1997年03月千葉大学
  • 1991年04月- 1995年03月千葉大学

学位

  • 理学博士(生物)

経歴

  • 2011年04月福井大学大学院工学研究科 准教授
  • 2008年11月- 2011年03月浜松医科大学分子イメージング先端研究センター 准教授
  • 2006年04月- 2008年01月三菱化学生命科学研究所 主任研究員
  • 2004年07月- 2006年03月自治医科大学分子病態治療研究センター 講師
  • 2000年07月- 2004年06月ハーバード大学医学部病理学研究科 研究員
  • 2000年03月- 2000年06月千葉大学理学部 助手
  • 1997年04月- 2000年03月日本学術振興会 特別研究員(DC1)

所属学協会

    日本神経化学会 評議員,盛和スカラーズソサエティ 一般会員,ナノ学会 一般会員,日本分子生物学会 一般会員,日本細胞生物学会 一般会員,日本神経科学会 一般会員,

研究活動情報

論文

  • Inhibition of glycogen synthase kinase-3 reduces extension of the axonal leading process by destabilizing microtubules in cerebellar granule neurons.
    Inami Y, Omura M, Kubota K, Konishi Y.
    Brain Res. 1690 51-60 2018年04月 査読有り
    Konishi Y
  • Differential retraction of axonal arbor terminals mediated by microtubule and kinesin motor
    Ikeno T, Konishi Y (corresponding author)
    Commun. Integr. Biol. e1288771 2017年02月 査読有り
  • Mechanisms of differential branch growth control in the single axonal arbor
    Konishi Y (corresponding author)
    Forma 32 S25-S28 2017年01月 査読有り
    コレスポンディングオーサー
  • Study of local intracellular signals regulating axonal morphogenesis using a microfluidic device
    Uryu D, Tamaru T, Suzuki A, Sakai R, Konishi Y (corresponding author)
    Sci. Technol. Adv. Mater. 17(1) 691-697 2016年10月 査読有り
    コレスポンディングオーサー
  • Kinesin-1 sorting in axons controls the differential retraction of arbor terminals.
    Seno T, Ikeno T, Mennya K, Kurishita M, Sakae N, Sato M, Takada H, Konishi Y (corresponding author)
    J Cell Sci. 29 3499-3510 2016年09月 査読有り
    コレスポンディングオーサー
  • Ttll9-/- mice sperm flagella show shortening of doublet 7, reduction of doublet 5 polyglutamylation and a stall in beating
    Konno A, Ikegami K, Konishi Y, Yang HJ, Abe M, Yamazaki M, Sakimura K, Yao I, Shiba K, Inaba K, Setou M
    J Cell Sci. 129 2757-2766 2016年07月 査読有り
  • DBZ regulates cortical cell positioning and neurite development by sustaining the anterograde transport of Lis1 and DISC1 through control of Ndel1 dual-phosphorylation
    M.Okamoto, T.Iguchi, T.Hattori, S.Matsuzaki, Y.Koyama, M.Taniguchi, M.Komada, M-J.Xie, H.Yagi, S.Simizu, Y.Konishi, M.Omi, T.Yoshimi, T.Tachibana, S.Fujieda, T.Katayama, A.Ito, S.Hirotsune, M.Tohyama, M.Sato
    J. Neurosci. 35(7) 2942-2958 2015年02月 査読有り
  • Cellular mechanisms for the axonal pattern formation: Initiation and branch morphogenesis
    Y.Konishi (corresponding author)
    Forma 29 51-54 2014年09月 査読有り
    コレスポンディングオーサー
  • A low-density culture method of cerebellar granule neurons with paracrine support applicable for the study of neuronal morphogenesis
    K Kubota, T Seno, Y Konishi
    Brain Res. 1539 15-23 2013年 査読有り
  • Axonal gradient of arachidonic acid-containing phosphatidylcholine and its dependence on actin dynamics
    Yang HJ, Sugiura Y, Ikegami K, Konishi Y, Setou M
    J Biol Chem. 287(8) 5290-5300 2012年 査読有り
  • Imaging mass spectrometry revealed the production of lyso-phosphatidylcholine in the injured ischemic rat brain
    Koizumi S, Yamamoto S, Hayasaka T, Konishi Y, Yamaguchi-Okada M, Goto-Inoue N, Sugiura Y, Setou M, Namba H
    Neuroscience 168 219-225 2010年 査読有り
  • Identification of tubulin deglutamylase among Caenorhabditis elegans and mammalian cytosolic carboxypeptidases (CCPs)
    Kimura Y, Kurabe N, Ikegami K, Tsutsumi K, Konishi Y, Kaplan OI, Kunitomo H, Iino Y, Blacque OE, Setou M
    J Biol Chem 285 22936-22941 2010年 査読有り
  • 神経細胞の形態制御に関わる細胞内在的分子機構
    小西 慶幸
    神経化学 49(4) 925-932 2010年 査読無し
  • 質量顕微鏡で生命の謎を解く
    大畑健次, 小西 慶幸, 瀬藤光利
    生物物理 52(2) 2010年 査読無し
  • Visualization of the cell-selective distribution of PUFA-containing phosphatidylcholines in mouse brain by imaging mass spectrometry
    Sugiura Y, Konishi Y, Zaima N, Kajihara S, Nakanishi H, Taguchi R, Setou M
    J Lipid Res 50 1776-1788 2009年 査読有り
  • Tubulin Tyrosination Navigates the Kinesin-1 Motor Domain to Axons
    Konishi Y, Setou M
    Nat Neurosci. 12 559-567 2009年 査読有り
  • 神経細胞の中にある交通標識
    小西 慶幸
    神経科学ニュース 176(4) 2009年 査読無し
  • Enhancement of Trk Signaling Pathways by the Cholestane Amide Conjugate MCC-257
    Yamada MK, Konishi Y, Kakinoki B, Ikegami K, Setou M
    J Pharmacol Sci. 108 131-134 2008年 査読有り
  • Imaging mass spectrometry technology and application on ganglioside study; visualization of age-dependent accumulation of C20-ganglioside molecular species in the mouse hippocampus
    Sugiura Y, Shimma S, Konishi Y, Yamada MK, Setou M
    PLoS ONE 3 e3232 2008年 査読有り
  • Transmembrane and ubiquitin-like domain-containing protein 1 (Tmub1/HOPS) facilitates surface expression of GluR2-containing AMPA receptors
    Yang H, Takagi H, Konishi Y, Ageta H, Ikegami K, Yao I, Sato S, Hatanaka K, Inokuchi K, Seog DH, Setou M
    PLoS ONE 3 e2809 2008年 査読有り
  • Activation of FOXO1 by Cdk1 in cycling cells and postmitotic neurons
    Yuan Z, Becker EB, Merlo P, Yamada T, DiBacco S, Konishi Y, Schaefer EM, Bonni A
    Science 319 1665-1668 2008年 査読有り
  • TGFbeta-Smad2 signaling regulates the Cdh1-APC/SnoN pathway of axonal morphogenesis
    Stegmuller J, Huynh MA, Yuan Z, Konishi Y, Bonni A
    J Neurosci. 28 1961-1969 2008年 査読有り
  • Six1 and Six4 promote survival of sensory neurons during early trigeminal gangliogenesis
    Konishi Y, Ikeda K, Iwakura Y, Kawakami K
    Brain Res. 1116 93-102 2006年 査読有り
  • Cell-intrinsic regulation of axonal morphogenesis by the Cdh1-APC target SnoN
    Stegmuller J, Konishi Y, Huynh MA, Yuan Z, Dibacco S, Bonni A
    Neuron 50 389-400 2006年 査読有り
  • Phosphorylation of BAD at Ser-128 during mitosis and paclitaxel-induced apoptosis
    Berndtsson M, Konishi Y, Bonni A, Hagg M, Shoshan M, Linder S, Havelka AM
    FEBS Lett. 579 3090-3094 2005年 査読有り
  • Cdh1-APC controls axonal growth and patterning in the mammalian brain
    Konishi Y, Stegmuller J, Matsuda T, Bonni S, Bonni A
    Science 303 1026-1030 2004年 査読有り
  • A CAMKII-NeuroD signaling pathway regulates dendritic morphogenesis
    Gaudilliere B, Konishi Y, de la Iglesia N, Yao G, Bonni A
    Neuron 41 229-241 2004年 査読有り
  • Characterization of a neurotrophin signaling mechanism that mediates neuron survival in a temporally specific pattern
    Shalizi A, Lehtinen M, Gaudilliere B, Donovan N, Han J, Konishi Y, Bonni A
    J Neurosci. 23 7326-7336 2003年 査読有り
  • The E2F-Cdc2 cell-cycle pathway specifically mediates activity deprivation-induced apoptosis of postmitotic neurons
    Konishi Y, Bonni A
    J Neurosci. 23 1649-1658 2003年 査読有り
  • Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain
    Matsu-ura T, Konishi Y, Aoki T, Naranjo JR, Mikoshiba K, Tamura T
    Brain Res Mol Brain Res. 109 198-206 2002年 査読有り
  • JNK phosphorylation and activation of BAD couples the stress-activated signaling pathway to the cell death machinery
    Donovan N, Becker EB, Konishi Y, Bonni A
    J Biol Chem. 277 40944-40949 2002年 査読有り
  • Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery
    Konishi Y, Lehtinen M, Donovan N, Bonni A
    Mol Cell 9 1005-1016 2002年 査読有り
  • Stimulation of gene expression of NeuroD-related factor in the mouse brain following pentylenetetrazol-induced seizures
    Konishi Y, Matsu-ura T, Mikoshiba K, Tamura T
    Brain Res Mol Brain Res. 97 129-136 2001年 査読有り
  • Promoter structure and gene expression of the mouse inositol 1,4,5-trisphosphate receptor type 3 gene
    Tamura T, Hashimoto M, Aruga J, Konishi Y, Nakagawa M, Ohbayashi T, Shimada M, Mikoshiba K
    Gene. 275 169-176 2001年 査読有り
  • Molecular cloning and characterization of neural activity-related RING finger protein (NARF): a new member of the RBCC family is a candidate for the partner of myosin V
    Ohkawa N, Kokura K, Matsu-Ura T, Obinata T, Konishi Y, Tamura T
    J Neurochem. 78 75-87 2001年 査読有り
  • Identification of the C-terminal activation domain of the NeuroD-related factor (NDRF)
    Konishi Y, Aoki T, Ohkawa N, Matsu-Ura T, Mikoshiba K, Tamura T
    Nucleic Acids Res. 28 2406-2412 2000年 査読有り
  • Distribution of AP-2 subtypes in the adult mouse brain
    Shimada M, Konishi Y, Ohkawa N, Ohtaka-Maruyama C, Hanaoka F, Makino Y, Tamura T
    Neurosci Res. 33 275-280 1999年 査読有り
  • Transcriptional regulation of mouse type 1 inositol 1,4,5-trisphosphate receptor gene by NeuroD-related factor
    Konishi Y, Ohkawa N, Makino Y, Ohkubo H, Kageyama R, Furuichi T, Mikoshiba K, Tamura T
    J Neurochem. 72 1717-1724 1999年 査読有り
  • Activation of the mouse inositol 1,4,5-trisphosphate receptor type 1 promoter by AP-2
    Ohkawa N, Konishi Y, Shimada M, Makino Y, Yoshikawa S, Mikoshiba K, Tamura T
    Gene 229 42327 1999年 査読有り
  • Transcription initiation sites and promoter structure of the mouse type 2 inositol 1,4,5-trisphosphate receptor gene
    Morikawa K, Ohbayashi T, Nakagawa M, Konishi Y, Makino Y, Yamada M, Miyawaki A, Furuichi T, Mikoshiba K, Tamura T
    Gene 196 181-185 1997年 査読有り
  • Demonstration of an E-box and its CNS-related binding factors for transcriptional regulation of the mouse type 1 inositol 1,4,5-trisphosphate receptor gene
    Konishi Y, Kobayashi Y, Kishimoto T, Makino Y, Miyawaki A, Furuichi T, Okano H, Mikoshiba K, Tamura T
    J Neurochem. 69 476-484 1997年 査読有り
  • Analysis of Glial-Specific Gene Expression Using in Vitro Transcription Assays
    Tamura T, Konishi Y, Makino Y, Mikoshiba K
    Methods 10 312-319 1996年 査読有り
  • Inhibition of glycogen synthase kinase-3 reduces extension of the axonal leading process by destabilizing microtubules in cerebellar granule neurons
    Inami, Yoshihiro;Omura, Mitsuru;Kubota, Kenta;Konishi, Yoshiyuki
    BRAIN RESEARCH 1690 51-60 2018年07月
  • Kinesin-1 sorting in axons controls the differential retraction of arbor terminals.
    Seno Takeshi;Ikeno Tatsuki;Mennya Kousuke;Kurishita Masayuki;Sakae Narumi;Sato Makoto;Takada Hiroki;Konishi Yoshiyuki
    Journal of cell science 129(18) 2016年
    :The ability of neurons to generate multiple arbor terminals from a single axon is crucial for establishing proper neuronal wiring. Although growth and retraction of arbor terminals are differentially regulated within the axon, the mechanisms by which neurons locally control their structure remain largely unknown. In the present study, we found that the kinesin-1 (Kif5 proteins) head domain (K5H) preferentially marks a subset of arbor terminals. Time-lapse imaging clarified that these arbor terminals were more stable than others, because of a low retraction rate. Local inhibition of kinesin-1 in the arbor terminal by chromophore-assisted light inactivation (CALI) enhanced the retraction rate. The microtubule turnover was locally regulated depending on the length from the branching point to the terminal end, but did not directly correlate with the presence of K5H. By contrast, F-actin signal values in arbor terminals correlated spatiotemporally with K5H, and inhibition of actin turnover prevented retraction. Results from the present study reveal a new system mediated by kinesin-1 sorting in axons that differentially controls stability of arbor terminals.
  • Study of local intracellular signals regulating axonal morphogenesis using a microfluidic device.
    Uryu Daiki;Tamaru Tomohiro;Suzuki Azusa;Sakai Rie;Konishi Yoshiyuki
    Science and technology of advanced materials 17(1) 2016年
    :The establishment and maintenance of axonal patterning is crucial for neuronal function. To identify the molecular systems that operate locally to control axonal structure, it is important to manipulate molecular functions in restricted subcellular areas for a long period of time. Microfluidic devices can be powerful tools for such purposes. In this study, we demonstrate the application of a microfluidic device to clarify the function of local Ca(2+) signals in axons. Membrane depolarization significantly induced axonal branch-extension in cultured cerebellar granule neurons (CGNs). Local application of nifedipine using a polydimethylsiloxane (PDMS)-based microfluidic device demonstrated that Ca(2+) entry from the axonal region via L-type voltage-dependent calcium channels (L-VDCC) is required for branch extension. Furthermore, we developed a method for locally controlling protein levels by combining genetic techniques and use of a microfluidic culture system. A vector for enhanced green fluorescent protein (EGFP) fused to a destabilizing domain derived from E. coli dihydrofolate reductase (ecDHFR) is introduced in neurons by electroporation. By local application of the DHFR ligand, trimethoprim (TMP) using a microfluidic device, we were able to manipulate differentially the level of fusion protein between axons and somatodendrites. The present study revealed the effectiveness of microfluidic devices to address fundamental biological issues at subcellular levels, and the possibility of their development in combination with molecular techniques.
  • Inhibition of glycogen synthase kinase-3 reduces extension of the axonal leading process by destabilizing microtubules in cerebellar granule neurons.
    Inami Yoshihiro;Omura Mitsuru;Kubota Kenta;Konishi Yoshiyuki
    Brain research 1690 2018年
    :Recent studies have uncovered various molecules that play key roles in neuronal morphogenesis. Nevertheless, the mechanisms underlying the neuron-type-dependent regulation of morphogenesis remain unknown. We have previously reported that inhibition of glycogen synthase kinase-3 (GSK3) markedly reduced axonal length of cerebellar granule neurons (CGNs) in a neuron-type-dependent manner. In the present study, we investigated the mechanisms by which the growth of CGN axons was severely suppressed upon GSK3 inhibition. Using time-lapse imaging of cultured CGNs at early morphogenesis, we found that extension of the leading process was severely inhibited by the pharmacological inhibition of GSK3. The rate of somal migration was also reduced with a GSK3 inhibitor in dissociated culture as well as in microexplant culture. In addition, CGNs ectopically expressed with a catalytically inactive mutant of GSK3 exhibited a migration defect in vivo. In axonal leading processes of CGNs, detyrosination and acetylation of α-tubulin, which are known to correlate with microtubule stability, were decreased by GSK3 inhibition. A photoconversion analysis found that inhibition of GSK3 increases the turnover of microtubules. Furthermore, in the presence of paclitaxel, a microtubule-stabilizing reagent, inhibition of GSK3 recovered the axonal leading process extension that was reduced by paclitaxel. Our results suggest that GSK3 supports the extension of axonal processes by stabilizing microtubules, contrary to its function in other neuron-types, lending mechanical insight into neuron-type-dependent morphological regulation.

著書

  • 遺伝子工学実験ノート(下巻)
    小西 慶幸
    編集
    プローブ作製法、リン酸カルシウム法、RNAiによる遺伝子抑制
    羊土社 2010年

講演・口頭発表等

  • 微小管と軸索輸送の制御を介した軸索形態の維持システム
    小西慶幸、池野龍輝、瀬野岳史、面谷耕佑、栗下雅行、栄成美、佐藤真、高田宗樹
    第121回 日本解剖学会総会・学術集会 2016年03月 選考無し
  • Spatial cell signaling mediated by microtubule regulations contributes to the maintenance of neuronal morphology
    小西 慶幸
    The 11th biennial meeting of APSN and the 55th annual meeting of JSN 2012年09月 選考有り 0
  • Tubulin polyglutamylation regulates cytoskeletal distribution in brain
    Ohata K, Konishi Y, Tsuchiya R, Ikegami K, Setou M
    第117回日本解剖学会総会・全国学術集会 2012年03月 選考有り 0
  • Local regulation of axonal transport and its possible contribution to the axonal branch pattering
    Y.Konishi
    International Symposium on Nanomedicine Molecular Science 2012年03月 選考無し 0
  • The Role of Plyglutamylation on the Regulation of Neuronal Cytoskeleton
    Ohata K, Konishi Y, Tsuchiya R, Ikegami K, Setou M
    The 51st ASCB annual meeting 2011年12月 選考有り 0
  • The regulation and function of post-translational modification of tubulins in neurons
    Konishi Y, Ohata K, Tsuchiya R, Ikegami K, Setou M
    The 6th International conference of Neurons and Brain Diseases 2011年08月 選考有り 0
  • The region specific control of branch stability in axonal arbors mediated by kinesin mediated transport
    Konishi Y, Seno T, Kubota K, Sakae N, Takada H
    9th International Symposium on Nanomedicine 2015年12月 選考無し

共同・受託研究希望(研究シーズ)登録

    神経細胞を用いた機能因子の評価等 小西 慶幸,

受賞

  •  日本神経化学会最優秀奨励賞2010年
  •  Harvard School of Public Health, Taplin fellowship2000年

科学研究費補助金

  • 軸索パターンの構築において空間情報伝達と構造的安定化を司る分子反応の解明新学術領域研究(研究領域提案型)(継続の研究領域・終了研究領域)
    代表者:小西 慶幸 2014年度
  • 微小管修飾を介した神経細胞の形態機能制御基盤研究(C)
    代表者:小西 慶幸 2014年度
  • 細胞内局所での分子反応と軸索変性との関連を明らかにする新学術領域研究(研究領域提案型)(継続の研究領域)
    代表者:小西 慶幸 2013年度
  • 微小管修飾を介した神経細胞の形態機能制御基盤研究(C)
    代表者:小西 慶幸 2013年度
  • 細胞内局所での分子反応と軸索変性との関連を明らかにする新学術領域研究(研究領域提案型)(継続の研究領域)
    代表者:小西 慶幸 2012年度
  • 微小管修飾を介した神経細胞の形態機能制御基盤研究(C)
    代表者:小西 慶幸 2012年度
  • 微小管修飾を介した神経細胞の形態機能制御基盤研究(C)
    代表者:小西 慶幸 2011年度

教育活動情報

担当授業

  • 生命科学トピックス
  • 知能システム工学実験Ⅱ
  • 計測工学
  • 知能システム工学特別演習及び実験Ⅰ
  • 知能システム工学特別演習及び実験Ⅱ
  • 脳神経構造学