掛川　渉 （カケガワ　ワタル）

Kakegawa, Wataru

写真a

所属（所属キャンパス）

医学部 生理学教室 （信濃町）

職名

准教授

外部リンク
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経歴 【 表示 ／ 非表示 】

  • 2016年07月
    -
    継続中

    慶應義塾大学, 医学部生理学Ｉ教室, 准教授

  • 2011年10月
    -
    2016年06月

    慶應義塾大学, 医学部生理学I教室, 専任講師

  • 2007年04月
    -
    2011年09月

    慶應義塾大学, 医学部生理学I教室, 助教

  • 2004年04月
    -
    2007年03月

    慶應義塾大学, 医学部生理学I教室, 助手

  • 2003年05月
    -
    2003年12月

    St. Jude Children's Research Hospital, Department of Developmental Neurobiology, Postdoc

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学歴 【 表示 ／ 非表示 】

  • 1999年04月
    -
    2003年03月

    群馬大学, 医学系研究科, 生理学

    大学院, 修了

  • 1997年04月
    -
    1999年03月

    群馬大学, 工学系研究科, 材料工学科

    大学院, 修了

  • 1993年04月
    -
    1997年03月

    群馬大学, 工学部, 材料工学科

    大学, 卒業

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学位 【 表示 ／ 非表示 】

  • 博士（医学）, 群馬大学, 課程, 2003年03月

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論文 【 表示 ／ 非表示 】

  • Hyaluronan synthesis supports glutamate transporter activity

    Hayashi M., Nishioka T., Shimizu H., Takahashi K., Kakegawa W., Mikami T., Hirayama Y., Koizumi S., Yoshida S., Yuzaki M., Tammi M., Sekino Y., Kaibuchi K., Shigemoto-Mogami Y., Yasui M., Sato K.

    Journal of Neurochemistry （Journal of Neurochemistry）  150 （ 3 ） 249 - 263 2019年08月

    研究論文（学術雑誌）,  ISSN  00223042

    　概要を見る

    © 2019 International Society for Neurochemistry Hyaluronan is synthesized, secreted, and anchored by hyaluronan synthases (HAS) at the plasma membrane and comprises the backbone of perineuronal nets around neuronal soma and dendrites. However, the molecular targets of hyaluronan to regulate synaptic transmission in the central nervous system have not been fully identified. Here, we report that hyaluronan is a negative regulator of excitatory signals. At excitatory synapses, glutamate is removed by glutamate transporters to turn off the signal and prevent excitotoxicity. Hyaluronan synthesized by HAS supports the activity of glial glutamate transporter 1 (GLT1). GLT1 also retracted from cellular processes of cultured astrocytes after hyaluronidase treatment and hyaluronan synthesis inhibition. A serial knockout study showed that all three HAS subtypes recruit GLT1 to cellular processes. Furthermore, hyaluronidase treatment activated neurons in a dissociated rat hippocampal culture and caused neuronal damage due to excitotoxicity. Our findings reveal that hyaluronan helps to turn off excitatory signals by supporting glutamate clearance. (Figure presented.). Cover Image for this issue: doi: 10.1111/jnc.14516.

  • Activity-Dependent Secretion of Synaptic Organizer Cbln1 from Lysosomes in Granule Cell Axons

    Ibata K., Kono M., Narumi S., Motohashi J., Kakegawa W., Kohda K., Yuzaki M.

    Neuron （Neuron）  102 （ 6 ） 1184 - 1198.e10 2019年06月

    研究論文（学術雑誌）,  ISSN  08966273

    　概要を見る

    © 2019 Elsevier Inc. Synapse formation is achieved by various synaptic organizers. Although this process is highly regulated by neuronal activity, the underlying molecular mechanisms remain largely unclear. Here we show that Cbln1, a synaptic organizer of the C1q family, is released from lysosomes in axons but not dendrites of cerebellar granule cells in an activity- and Ca2+-dependent manner. Exocytosed Cbln1 was retained on axonal surfaces by binding to its presynaptic receptor neurexin. Cbln1 further diffused laterally along the axonal surface and accumulated at boutons by binding postsynaptic δ2 glutamate receptors. Cbln1 exocytosis was insensitive to tetanus neurotoxin, accompanied by cathepsin B release, and decreased by disrupting lysosomes. Furthermore, overexpression of lysosomal sialidase Neu1 not only inhibited Cbln1 and cathepsin B exocytosis in vitro but also reduced axonal bouton formation in vivo. Our findings imply that co-release of Cbln1 and cathepsin B from lysosomes serves as a new mechanism of activity-dependent coordinated synapse modification. Ibata et al. find that Cbln1 is released from lysosomes by neuronal activity and accumulated at axonal boutons of cerebellar granule cells. Co-release of Cbln1 and lysosomal enzymes may serve as a new mechanism of activity-dependent coordinated synapse modification.

  • Mice lacking EFA6C/Psd2, a guanine nucleotide exchange factor for Arf6, exhibit lower Purkinje cell synaptic density but normal cerebellar motor functions

    Saegusa S., Fukaya M., Kakegawa W., Tanaka M., Katsumata O., Sugawara T., Hara Y., Itakura M., Okubo T., Sato T., Yuzaki M., Sakagami H.

    PLoS ONE （PLoS ONE）  14 （ 5 ）  2019年05月

    研究論文（学術雑誌）

    　概要を見る

    © 2019 Saegusa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ADP ribosylation factor 6 (Arf6) is a small GTPase that regulates various neuronal events including formation of the axon, dendrites and dendritic spines, and synaptic plasticity through actin cytoskeleton remodeling and endosomal trafficking. EFA6C, also known as Psd2, is a guanine nucleotide exchange factor for Arf6 that is preferentially expressed in the cerebellar cortex of adult mice, particularly in Purkinje cells. However, the roles of EFA6C in cerebellar development and functions remain unknown. In this study, we generated global EFA6C knockout (KO) mice using the CRISPR/Cas9 system and investigated their cerebellar phenotypes by histological and behavioral analyses. Histological analyses revealed that EFA6C KO mice exhibited normal gross anatomy of the cerebellar cortex, in terms of the thickness and cellularity of each layer, morphology of Purkinje cells, and distribution patterns of parallel fibers, climbing fibers, and inhibitory synapses. Electron microscopic observation of the cerebellar molecular layer revealed that the density of asymmetric synapses of Purkinje cells was significantly lower in EFA6C KO mice compared with wild-type control mice. However, behavioral analyses using accelerating rotarod and horizontal optokinetic response tests failed to detect any differences in motor coordination, learning or adaptation between the control and EFA6C KO mice. These results suggest that EFA6C plays ancillary roles in cerebellar development and motor functions.

  • Interneuronal NMDA receptors regulate long-term depression and motor learning in the cerebellum

    Kono M., Kakegawa W., Yoshida K., Yuzaki M.

    Journal of Physiology （Journal of Physiology）  597 （ 3 ） 903 - 920 2019年02月

    研究論文（学術雑誌）, 共著,  ISSN  00223751

    　概要を見る

    © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society Key points: NMDA receptors (NMDARs) are required for long-term depression (LTD) at parallel fibre–Purkinje cell synapses, but their cellular localization and physiological functions in vivo are unclear. NMDARs in molecular-layer interneurons (MLIs), but not granule cells or Purkinje cells, are required for LTD, but not long-term potentiation induced by low-frequency stimulation of parallel fibres. Nitric oxide produced by NMDAR activation in MLIs probably mediates LTD induction. NMDARs in granule cells or Purkinje cells are dispensable for motor learning during adaptation of horizontal optokinetic responses. Abstract: Long-term potentiation (LTP) and depression (LTD), which serve as cellular synaptic plasticity models for learning and memory, are crucially regulated by N-methyl-d-aspartate receptors (NMDARs) in various brain regions. In the cerebellum, LTP and LTD at parallel fibre (PF)–Purkinje cell (PC) synapses are thought to mediate certain forms of motor learning. However, while NMDARs are essential for LTD in vitro, their cellular localization remains controversial. In addition, whether and how NMDARs mediate motor learning in vivo remains unclear. Here, we examined the contribution of NMDARs expressed in granule cells (GCs), PCs and molecular-layer interneurons (MLIs) to LTD/LTP and motor learning by generating GC-, PC- and MLI/PC-specific knockouts of Grin1, a gene encoding an obligatory GluN1 subunit of NMDARs. While robust LTD and LTP were induced at PF–PC synapses in GC- and PC-specific Grin1 (GC-Grin1 and PC-Grin1, respectively) conditional knockout (cKO) mice, only LTD was impaired in MLI/PC-specific Grin1 (MLI/PC-Grin1) cKO mice. Application of diethylamine nitric oxide (NO) sodium, a potent NO donor, to the cerebellar slices restored LTD in MLI/PC-Grin1 cKO mice, suggesting that NO is probably downstream to NMDARs. Furthermore, the adaptation of horizontal optokinetic responses (hOKR), a cerebellar motor learning task, was normally observed in GC-Grin1 cKO and PC-Grin1 cKO mice, but not in MLI/PC-Grin1 cKO mice. These results indicate that it is the NMDARs expressed in MLIs, but not in PCs or GCs, that play important roles in LTD in vitro and motor learning in vivo.

  • PhotonSABER: new tool shedding light on endocytosis and learning mechanisms in vivo

    Matsuda S., Kakegawa W., Yuzaki M.

    Communicative and Integrative Biology （Communicative and Integrative Biology）  12 （ 1 ） 34 - 37 2019年01月

    研究論文（学術雑誌）

    　概要を見る

    © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. In the central nervous system, activity-dependent endocytosis of postsynaptic AMPA-type glutamate receptors (AMPA receptors) is thought to mediate long-term depression (LTD), which is a synaptic plasticity model in various neuronal circuits. However, whether and how AMPA receptor endocytosis and LTD at specific synapses are causally linked to learning and memory in vivo remains unclear. Recently, we developed a new optogenetic tool, PhotonSABER, which could control AMPA receptor endocytosis in temporal, spatial, and cell-type-specific manners at activated synapses. Using PhotonSABER, we found that AMPA receptor endocytosis and LTD at synapses between parallel fibers and Purkinje cells in the cerebellum mediate oculomotor learning. We also found that PhotonSABER could inhibit endocytosis of epidermal growth factor receptors in HeLa cells upon light stimulation. These results demonstrate that PhotonSABER is a powerful tool for analyzing the physiological functions of endocytosis in non-neuronal cells, as well as the roles of LTD in various brain regions.

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競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 分泌性C1qファミリー分子との相互作用がもたらすカイニン酸受容体の新しい機能

    2024年04月
    -
    2027年03月

    掛川 渉, 基盤研究(B), 補助金,  研究代表者

  • イオンチャネル型グルタミン酸受容体の新規活動様式の解明：KA受容体をモデルとして

    2022年06月
    -
    2024年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 掛川 渉, 挑戦的研究（萌芽）, 補助金,  研究代表者

  • Naked spineから読み解く小脳シナプスの新しい形成・動作原理

    2020年04月
    -
    2024年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 掛川 渉, 基盤研究(B), 補助金,  研究代表者

  • 新規ケモジェネティクス法による脳内記憶・学習回路の制御と理解

    2020年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 掛川 渉, 新学術領域研究（研究領域提案型）, 補助金,  研究代表者

  • 脳内夾雑環境で働く記憶・学習回路の新規化学遺伝学的制御

    2018年04月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 掛川　渉, 新学術領域研究(研究領域提案型), 補助金,  研究代表者

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受賞 【 表示 ／ 非表示 】

  • 日本D-アミノ酸学会奨励賞

    掛川 渉, 2014年09月, 日本D-アミノ酸学会

    受賞区分： 国内学会・会議・シンポジウム等の賞

  • 入澤宏・彩記念若手奨励賞

    掛川 渉, 2013年03月, 日本生理学会

    受賞区分： 国内学会・会議・シンポジウム等の賞

  • 文部科学大臣賞表彰若手科学者賞

    掛川 渉, 2012年04月, 文部科学省, グルタミン酸受容体による記憶学習制御の研究

    受賞区分： その他

  • 慶應義塾大学医学部三四会奨励賞

    掛川 渉, 2011年11月, 慶應義塾大学医学部三四会, D-セリン－グルタミン酸受容体シグナリングによるシナプス可塑性および記憶学習制御

    受賞区分： その他

  • 日本生理学会奨励賞

    掛川 渉, 2008年03月, 日本生理学会, シナプス伝達・可塑性を制御するグルタミン酸受容体機能の解明

    受賞区分： 国内学会・会議・シンポジウム等の賞

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担当授業科目 【 表示 ／ 非表示 】

  • 生理学Ⅱ

    2024年度

  • 生理学Ⅰ

    2024年度

  • 生理学Ⅱ

    2023年度

  • 生理学Ⅰ

    2023年度

  • 生理学Ⅱ

    2022年度

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