SUZUKI Takeshi

写真a

Affiliation

Medical Development Center Dean, Department of Liberal Arts and Sciences, Biology

Job title

Associate Professor

Homepage URL

http://web.sapmed.ac.jp/biol/index.html

Education 【 display / non-display

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    1994

    The University of Tokyo   Graduate School, Division of Science  

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    1994

    The University of Tokyo   理学系研究科   生物科学専攻  

Professional Memberships 【 display / non-display

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    日本解剖学会

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    日本組織細胞化学会

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    日本細胞生物学会

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    The American Society for Cell Biology

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    日本顕微鏡学会

Research Areas 【 display / non-display

  • Life sciences   Anatomy  

Affiliation 【 display / non-display

  • Sapporo Medical University   Center for Medical Education Biology   Associate Professor  

 

Research Interests 【 display / non-display

  • 超分子複合体

  • 糖輸送体

  • 膜タンパク質

  • ライブセルイメージング

  • ライブセルイメージング

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Papers 【 display / non-display

  • Caveolae-mediated endocytosis pathway regulates endothelial fenestra homeostasis in the rat pituitary.

    Takashi Nakakura, Hideyuki Tanaka, Takeshi Suzuki

    Biochemical and biophysical research communications   675   177 - 183  2023.07  [International journal]

     View Summary

    Endothelial fenestrae are transcellular pores separated by diaphragms formed by plasmalemma vesicle-associated proteins (PLVAP) and function as channels for peptide hormones and other substances. Caveola, a key regulator of clathrin-independent endocytosis, may be involved in the invagination and fusion of plasma membranes, which are essential for fenestra formation. In this study, we first found that caveolin-1 and -2, the major components of caveolae, was localized in fenestrated endothelial cells in the anterior lobe of the rat pituitary by immunohistochemistry. As we also observed caveolae in the endothelial cells of the anterior lobe of the rat pituitary by transmission electron microscopy, we studied the relationship between the caveolae-mediated endocytosis pathway and fenestrae structure in cultured endothelial cells isolated from the anterior lobe of the rat pituitary (CECAL) by immunofluorescence staining and scanning electron microscopy. The inhibition of caveolae-mediated endocytosis by genistein enlarged the PLVAP-positive oval-shaped structure that represented the sieve plate and induced the formation of a doughnut-shaped bulge around the fenestra in CECAL. In contrast, the acceleration of caveolae-mediated endocytosis by okadaic acid induced the diffusion of PLVAP-positive signals in the cytoplasm and reduced the number of fenestrae in CECAL. These results indicate that the caveolae-mediated endocytosis pathway is involved in the fenestra homeostasis in the fenestrated endothelial cells of the rat pituitary.

    DOI PubMed

  • Regulation of fenestra formation via actin-dynamin2 interaction in rat pituitary endothelial cells

    Takashi Nakakura, Hideyuki Tanaka, Takeshi Suzuki

    Cell and Tissue Research ( Springer Science and Business Media LLC )   2022.09

    DOI

  • Fibronectin-integrin signaling regulates PLVAP localization at endothelial fenestrae by microtubule stabilization.

    Takashi Nakakura, Takeshi Suzuki, Kotaro Horiguchi, Hideyuki Tanaka, Kenjiro Arisawa, Toshio Miyashita, Yoko Nekooki-Machida, Haruo Hagiwara

    Cell and tissue research   384 ( 2 ) 449 - 463  2021.05  [International journal]

     View Summary

    Endothelial fenestrae are the transcellular pores existing on the capillary walls which are organized in clusters referred to as sieve plates. They are also divided by a diaphragm consisting of plasmalemma vesicle-associated protein (PLVAP). In this study, we examined the involvement of fibronectin signaling in the formation of fenestra and diaphragm in endothelial cells. Results showed that Itga5 and Itgb1 were expressed in PECAM1-positive endothelial cells isolated from the anterior lobe (AL) of the rat pituitary, and integrin α5 was localized at the fenestrated capillaries of the rat pituitary and cultured PECAM1-positive endothelial cells isolated from AL (CECAL). Inhibition of both integrin α5β1 and FAK, a key molecule for integrin-microtubule signaling, respectively, by ATN-161 and FAK inhibitor 14, caused the delocalization of PLVAP at the sieve plates and depolymerization of microtubules in CECAL. Paclitaxel prevented the delocalization of PLVAP by the inhibition of integrin α5β1. Microtubule depolymerization induced by colcemid also caused the delocalization of PLVAP. Treatment of CECAL with ATN-161 and colcemid caused PLVAP localization at the Golgi apparatus. The localization of PLVAP at the sieve plates was inhibited by BFA treatment in a time-dependent manner and spread diffusely to the cytoplasm. These results indicate that a constant supply of PLVAP proteins by the endomembrane system via the Golgi apparatus is essential for the localization of PLVAP at sieve plates. In conclusion, the endomembrane transport pathway from the Golgi apparatus to sieve plates requires microtubule cytoskeletons, which are regulated by fibronectin-integrin α5β1 signaling.

    DOI PubMed

  • Fibronectin is essential for formation of fenestrae in endothelial cells of the fenestrated capillary.

    Takashi Nakakura, Takeshi Suzuki, Hideyuki Tanaka, Kenjiro Arisawa, Toshio Miyashita, Yoko Nekooki-Machida, Toshiki Kurosawa, Yuma Tega, Yoshiharu Deguchi, Haruo Hagiwara

    Cell and tissue research   383 ( 2 ) 823 - 833  2021.02  [International journal]

     View Summary

    Endothelial fenestrae are transcellular pores that pierce the capillary walls in endocrine glands such as the pituitary. The fenestrae are covered with a thin fibrous diaphragm consisting of the plasmalemma vesicle-associated protein (PLVAP) that clusters to form sieve plates. The basal surface of the vascular wall is lined by basement membrane (BM) composed of various extracellular matrices (ECMs). However, the relationship between the ECMs and the endothelial fenestrae is still unknown. In this study, we isolated fenestrated endothelial cells from the anterior lobe of the rat pituitary, using a dynabeads-labeled antibody against platelet endothelial cell adhesion molecule 1 (PECAM1). We then analyzed the gene expression levels of several endothelial marker genes and genes for integrin α subunits, which function as the receptors for ECMs, by real-time polymerase chain reaction (PCR). The results showed that the genes for the integrin α subunit, which binds to collagen IV, fibronectin, laminin-411, or laminin-511, were highly expressed. When the PECAM1-positive cells were cultured for 7 days on collagen IV-, fibronectin-, laminins-411-, or laminins-511-coated coverslips, the sieve plate structures equipped with probably functional fenestrae were maintained only when the cells were cultured on fibronectin. Additionally, real-time PCR analysis showed that the fibronectin coating was effective in maintaining the expression pattern of several endothelial marker genes that were preferentially expressed in the endothelial cells of the fenestrated capillaries. These results indicate that fibronectin functions as the principal factor in the maintenance of the sieve plate structures in the endothelial cells of the fenestrated capillary.

    DOI PubMed

  • ATAT1 is essential for regulation of homeostasis-retaining cellular responses in corticotrophs along hypothalamic-pituitary-adrenal axis

    Takashi Nakakura, Takeshi Suzuki, Seiji Torii, Anshin Asano-Hoshino, Yoko Nekooki-Machida, Hideyuki Tanaka, Kenjiro Arisawa, Yoshimi Nishijima, Takao Susa, Tomoki Okazaki, Yoshiko Kiuchi, Haruo Hagiwara

    CELL AND TISSUE RESEARCH ( SPRINGER )  370 ( 1 ) 169 - 178  2017.10  [Refereed]

     View Summary

    The production and secretion of adrenocorticotropin, a proopiomelanocortin (POMC)-derived hormone, by corticotrophs in the anterior pituitary, is regulated by corticotrophin-releasing hormone (CRH) and glucocorticoids. We have previously demonstrated that adrenalectomy induces a-tubulin N-acetyltransferase 1 (ATAT1) expression and atubulin acetylation in corticotrophs. However, the regulatory mechanism of ATAT1 expression and the function of acetylated microtubules in corticotrophs are unclear. Here, we analyze the effect of CRH or dexamethasone on Atat1 expression in the mouse corticotroph AtT20 cell line. The expression of Atat1 was increased by CRH and decreased by dexamethasone in AtT20 cells. We examined the effect of Atat1 knockdown on the expression of POMC-associated genes and the dexamethasone-induced nuclear translocation of glucocorticoid receptor (GR) by real-time polymerase chain reaction and Western blot analysis, respectively. Atat1 knockdown resulted in a significant increase in the expression of ACTH-producing genes and decreased the dexamethasone-induced nuclear translocation of GR accompanied with a reduction in a-tubulin acetylation. Atat1 overexpression resulted in a significant increase in a-tubulin acetylation and the dexamethasone-induced nuclear translocation of GR. These results suggest that the acetylated microtubules function as the rail-line for the transportation of GR into the nucleus. We conclude that ATAT1 finely tunes the cellular responses of corticotrophs to hormonal stimulation through an intracellular feedback circuit.

    DOI PubMed

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Books and Other Publications 【 display / non-display

  • バイオイメージングで知っておきたい顕微鏡の基礎

    鈴木 健史(pp. 143-158)

    日本組織細胞化学会編、組織細胞化学2012  2012

  • 共焦点レーザー顕微鏡および蛍光顕微鏡を使いこなすための基礎知識

    鈴木 健史( Part: Contributor, pp. 103-115)

    日本組織細胞化学会編、組織細胞化学2011  2011.08

  • Double-label immunoelectron microscopy for studying the colocalization of proteins in cultured cells.

    Immunoelectron microscopy, Methods in Molecular Biology 657, Schwartzbach and Osafune (eds), Springer Science+Business Media, New York  2010

  • Double-label immunoelectron microscopy for studying the colocalization of proteins in cultured cells.

    Immunoelectron microscopy, Methods in Molecular Biology 657, Schwartzbach and Osafune (eds), Springer Science+Business Media, New York  2010

  • Double-label immunoelectron microscopy for studying the colocalization of proteins in culture cells.

    H Hagiwara, T Aoki, T Suzuki, K Takata( Part: Joint author, Schwartzbach SD, Osafune T, eds, Immunoelectron microscopy, methods and protocols)

    New York: Human Press  2010

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Misc 【 display / non-display

  • 線維芽細胞における一次線毛伸長について

    萩原治夫, 中倉敬, 浅野安信, 有澤謙二郎, 田中秀幸, 鈴木健史

    日本臨床分子形態学会総会・学術集会講演プログラム・要旨集   45th   98  2013

    J-GLOBAL

  • 頂部膜剥離法によって作製した試料によるAQP2動態の観察

    青木武生, 萩原治夫, 鈴木健史, 松崎利行, 高田邦昭

    解剖学雑誌   85 ( Supplement )  2010

    J-GLOBAL

  • Double-label immunoelectron microscopy for studying the colocalization of proteins in cultured cells

    Hagiwara H, Aoki T, Suzuki T, Takata K

    Methods in Molecular Biology   657   249 - 57  2010

    DOI

  • Pre-embedding immunoelectron microscopy of chemically fixed mammalian tissue culture cells

    Hagiwara H, Aoki T, Suzuki T, Takata K

    Methods in Molecular Biology   657   145 - 54  2010

    DOI

  • Roles of gap junctions in glucose transport from glucose transporter 1-positive to -negative cells in the lateral wall of the rat cochlea

    Toshihiro Suzuki, Tatsuya Matsunami, Yasuo Hisa, Kuniaki Takata, Tetsuro Takamatsu, Masahito Oyamada

    HISTOCHEMISTRY AND CELL BIOLOGY ( SPRINGER )  131 ( 1 ) 89 - 102  2009.01

     View Summary

    Despite the importance of glucose metabolism for auditory function, the mechanisms of glucose transport in the cochlea are not completely understood. We hypothesized that gap junctions mediate intercellular glucose transport in the cochlea in cooperation with facilitative glucose transporter 1 (GLUT1). Immunohistochemistry showed that GLUT1 and the tight junction protein occludin were expressed in blood vessels, and GLUT1, the gap junction proteins connexin26 and connexin30, and occludin were also present in strial basal cells in the lateral wall of the rat cochlea. Gap junctions were found among not only these GLUT1-positive strial basal cells but also GLUT1-negative fibrocytes in the spiral ligaments and strial intermediate cells. Glucose imaging using 6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-6-deoxyglucose (6-NBDG, MW 342) together with Evans Blue Albumin (EBA, MW 68,000) showed that 6-NBDG was rapidly distributed throughout the stria vascularis and spiral ligament, whereas EBA was localized only in the vessels. The gap junctional uncouplers heptanol and carbenoxolone inhibited the distribution of 6-NBDG in the spiral ligament without decreasing the fluorescence of EBA in the blood vessels. These findings suggest that gap junctions mediate glucose transport from GLUT1-positive cells (strial basal cells) to GLUT1-negative cells (fibrocytes in the spiral ligament and strial intermediate cells) in the cochlea.

    DOI

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Industrial Property Rights 【 display / non-display

  • 顕微鏡装置及びそれを用いた蛍光観察方法

    特許第4288323号

    五十嵐康伸, 出口雄規, 鈴木健史, 橋本浩一

    Patent

  • 温水循環式顕微培養チャンバー

    特許特許第4117341号

    鈴木 健史

    Patent

Awards 【 display / non-display

  • ベストティーチャー賞

    2013.03   札幌医科大学  

    Winner: 鈴木 健史

  • ベストティーチャー優秀賞

    2011.05   群馬大学  

    Winner: 鈴木 健史

  • ベストティーチャー石井賞

    2010.12   群馬大学医学部  

    Winner: 鈴木 健史

  • 日本組織細胞化学会論文賞

    2006  

  • JSHC Young Investigator Award

    2006  

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Research Projects 【 display / non-display

  • The mechanism of elongation of primary cilia from basal bodies in ciliogenesis

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2012
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    2014
     

    HAGIWARA Haruo, SUZUKI Takeshi, ARISAWA Kenjiro, ASANO Anshin, NAKAKURA Takashi

    Authorship: Collaborating Investigator(s) (not designated on Grant-in-Aid)

     View Summary

    Primary cilia, an organelle found on nearly every cell in the human body, contain an axoneme, which is composed of microtubules and their associated structures. Lithium ion is known to promote the elongation of primary cilia in a variety of cell types, but it is unknown whether lithium is involved in the acetylation of alpha-tubulin in cilia. Because the acetylation of alpha-tubulin may be important for the elongation of primary cilia, in this study we examined the effects of lithium chloride (LiCl) treatments on the acetylation of alpha-tubulin and length of primary cilia in human fibroblast KD cells. We also investigated the involvement of alphaTAT1 (alpha-tubulin N-acetyltransferase 1) in the signaling pathway mediating glycogen synthase kinase-3beta(GSK-3beta) and adenylate cyclase III. Our results suggested that LiCl treatments activate alphaTAT1 by the inhibition of GSK-3 beta and promote the alpha-tubulin acetylation, and then elongate the primary cilia.

  • Analysis of endosome/post-endosome system with special reference to water channel aquaporin 2

    基盤研究(B)

    Project Year :

    2006
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    2009
     

    Kuniaki TAKATA, 鈴木 健史, 萩原 治夫, 青木 武生, 松崎 利行, Takeshi SUZUKI, TOSHIYUKI MATSUZAKI, Haruo HAGIWARA, Takeo AOKI

    Authorship: Collaborating Investigator(s) (not designated on Grant-in-Aid)

     View Summary

    Vesicular trafficking that determines the number of cell surface molecules serves as one of important regulatory mechanisms found in the control of the reabsorption of water in the kidney, maintenance of blood glucose level, etc.Intracellular vesicles involved in the endocytosis and subsequent recycling process, such as endosomes and post-endosomal vesicles are key components in such vesicular trafficking and storage. We used water channel aquaporin 2 whose trafficking is regulated by hypophysial hormone vasopressin. Glucose transporter 4(GLUT4), whose trafficking is regulated by insulin in adipocytes and muscle cells, was coexpressed with aquaporin 2 in MDCK cells, and their localization was visualized by immunofluorescence and GFP-tagging methods. Aquaporin 2 and GLUT4 exhibited distinct localization pattern each other in both the resting and stimulated states, showing that aquaporin 2 and GLUT4 are stored in distinct post-endosomal compartments each other, and that their trafficking is differentially regulated. Translocation of aquaporin 2 has been considered to be regulated by its phosphorylation. We raised antibodies that specifically detect phosphorylated aquaporin 2. By western blotting and immunofluorescence microscopy, phosphorylation of aquaporin 2 was found not only on the cell surface but also intracellular vesicles, suggesting the ubiquitous presence of phosphorylated aquaporin 2.

  • ライブセルイメージングによる上皮細胞の細胞極性形成機構の解析

    Project Year :

    2004
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    2006
     

  • ライブセルイメージングによる上皮細胞の細胞極性形成機構の解析

    Project Year :

    2004
    -
    2006
     

  • ライブセルイメージングによる上皮細胞の細胞極性形成機構の解析

    若手研究(A)

    Project Year :

    2004
    -
    2006
     

    鈴木 健史

    Authorship: Principal investigator

     View Summary

    細胞極性構築過程における膜タンパク質の局在動態を3次元ライブセルイメージングにより解析した.タイトジャンクションフレームワークの構築過程におけるSGLTの分子局在動態をライブセル解析したところ,細胞極性のない状態の細胞で細胞膜全周に発現しているSGLT分子が,タイトジャンクションの完成にともない頂部細胞膜に徐々に濃縮され最終的に頂部細胞膜に限局した局在にシフトしていく様子を,同一の細胞で初めて確認できた.このSGLTの頂部細胞膜への移行や選択的局在に膜脂質が関与している可能性について検討した.コレステロールを急激に除去すると30分でSGLTが細胞膜全周に移行した.この際,タイトジャンクションに変化はなくコレステロールの過剰投与によって相殺されることから,SGLTの頂部細胞膜局在にコレステロールが重要であることを明らかにした.また,コルセミド添加により微小管を脱重合させた場合もSGLTの細胞膜全周への移行が起こることを発見した.この際もタイトジャンクションに変化はなく,上皮細胞シートの電気抵抗性や,他の頂部細胞膜マーカータンパクの染色性に変化がないことから,細胞間接着が壊れた結果の側方拡散による細胞膜全周への移行ではないことを確認した.培地中のコルセミドを洗い流し,通常の培地で培養すると微小管系の復元にともない徐々にSGLTの頂部細胞膜局在が復活する様子も確認した.以上の結果は,微小管系がSGLTの頂部細胞膜局在の維持に機能していることを示している.また,細胞極性は隣接する細胞との接触が引き金となって形成されるが,この細胞接触面にPIP3が一過的に出現することを見いだしている.また,免疫細胞の細胞極性形成過程におけるシグナル分子の動態もライブセルイメージングにより解析し,免疫シナプスにPKCやPIP3,DAGなどの様々なシグナル分子が集合する様子をとらえることに成功した.

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Presentations 【 display / non-display

  • 初期エンドソーム蛋白質EEA1と内在化カベオラとの関連性

    日本組織細胞化学会第42回総会・学術集会 

    Presentation date: 2001

  • ラット乳腺における水チャネルAQP1およびAQP3の局在

    第45回日本組織細胞化学会総会・学術集会 

    Presentation date: 2004

  • Role of early endosomes in caevolar internalization in endothelial cells

    16th International Congress of the IFAA 

    Presentation date: 2004

  • デコンボリューション顕微鏡法。

    日本顕微鏡学会第61回学術講演会 

    Presentation date: 2005

  • アクアポリン2水チャネルの細胞内貯蔵部位と細胞内動態

    第111回日本解剖学会総会・全国学術集会 

    Presentation date: 2006

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Teaching Experience 【 display / non-display

  • 解剖生理学  

    前橋看護学院  

  • 基礎生物学  

    札幌医科大学  

  • 神経解剖学  

    群馬大学  

  • 生物学  

    札幌医科大学  

  • 組織実習  

    群馬大学  

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Committee Memberships 【 display / non-display

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      評議員