Welcome to Sakagami Lab at Kitasato University

業績リスト

業績リスト (北里大学着任2009年以降)(数字は大学院時代からの論文の通し番号)
2024年red
(183) Fukaya M, Ibuchi K, Itakura M, Shiroshima T, Hara Y, Sugawara T, Frédéric Luton,
   Sakagami H.
   EFA6A, an exchange factor for Arf6, regulates NGF-dependent TrkA recycling from early
   endosomes and neurite outgrowth in PC12 cells.
   Traffic (2023) in press

Traffic3.jpg

   EFA6A-Arf6経路がPC12細胞の早期エンドソームにおいて、NGF刺激依存的な細胞膜への
   TrkAのリサイクリングに関与すること、EFA6AがTrkAと複合体を形成することにより、
   積荷タンパク質であるTrkAの近くでArf6を活性化することを見出しました。
   また、EFA6A-Arf小胞輸送経路によるNGF-TrkAシグナル制御が
   初代脊髄神経節の感覚ニューロンにおいても起こっていることを見出しました。
(182) Nakashima M, Shiroshima T, Fukaya M, Sugawara T, Sakagami H, Yamazawa K.
  C-terminal truncations in IQSEC2: implications for synaptic localization, guanine nucleotide
   exchange factor activity, and neurological manifestations.
  J. Hum. Genet. (2024) in press

J Hum Genet2024.jpg

   Arf6-GEFファミリーのIQSEC2/BRAG2 (IQ-ArfGEF)を原因遺伝子とする先天性知的障害の
   新たな遺伝子変異としてのC末領域Q1227のナンセンス突然変異の症例報告。変異により
   終止コドンが挿入され発現しなくなったIQSEC2のC末領域には、IRSp53やPSD-95との
   結合領域を含み、図で示すようにIQSEC2(Q1227*)はシナプス局在能を失う。
   高次神経機能におけるIQSEC2のシナプス後肥厚部での局在の重要性が示唆された。
2023年red

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(181) Hara Y, Katsuyama T, Fukaya M,
   Sugawara T, Shiroshima T, Sadakata T,
   Osumi N, Sakagami H.
   ADP ribosylation factor 4 (Arf4) regulates
   radial migration through N-cadherin trafficking
  during cerebral cortical development.
  eNeuro 10:ENEURO.0125-23.2023 (2023)
  クラスII Arfファミリーに属するArf4が、大脳皮質
  層形成過程の多極性移動とロコーモーション
  に、N-cadherinの細胞内トラッフィキングを介し
  て制御することを明らかにしました。この結果、クラスIIのArf4とクラスIIIのArf6が
  それぞれN-cadherinのTGNへの逆行性輸送と細胞膜へのリサイクリング経路
  の異なる段階の制御を通して神経細胞移動に関与することが示唆されました。
(180) Pakkarato S, Sakagami H, Watanabe M, Kondo H, Hipkaeo W, Chomphoo S.
  Discrete localization patterns of PIP5Kγ and PLCβ3 working sequentially in
  phosphoinositide-cycle within mouse sensory neuron somata
  Microsc. Res. Tech 86:351-358 (2023)

2022年red
(179) Ito A, Fukaya M, Sakagami H.
  Physiological and Pathological Roles of the Cytohesin Family in Neurons.
  Int. J. Mol. Sci. 23:5087 (2022) . doi: 10.3390/ijms23095087
  Cytohesinを介するArf経路の神経細胞における生理的役割と病態への関与に関する総説
(178) Tokumitsu H, Sakagami H.
  Molecular mechanisms underlying Ca2+/calmodulin-dependent protein kinase kinase signal
  transduction.
  Int. J. Mol. Sci. 23:11025 (2022)
(177) Kim D, Jung H, Shirai Y, Kim H, Kim J, Lim D, Mori T, Lee H, Park D, Kim HY, Guo Q,
  Pang B, Qiu W, Kouyama-Suzuki E, Uemura T, Kasem E, Fu Y, Kim S, Tokunaga A,
  Yoshizawa T, Suzuki T, Sakagami H, Lee KJ, Ko J, Tabuchi K, Um JE.
  IQSEC3 Deletion Impairs fear memory through upregulation of ribosomal S6K1 signaling in
  the hippocampus.
  Biol. Psych. 91:821-831 (2022)
(176) Hashimoto Y, Kuniishi H, Sakai K, Fukushima Y, Du X, Yamashiro K, Hori K, Imamura M,
  Hoshino M, Yamada M, Araki T, Sakagami H, Takeda S, Itaka K, Ichinohe N, Muntoni F,
  Sekiguchi M, Aoki Y.,
  Brain Dp140 alters glutamatergic transmission and social behaviour in the mdx52 mouse
  model of Duchenne muscular dystrophy.
  Prog. Neurobiol. 216:102288 (2022)
(175) Kaneshige R , Ohtsuka S, Harada Y, Kawamata I, Magari M, Kanayama N, Hatano N,
  Sakagami H, Tokumitsu H.
  Substrate recognition by Arg/Pro-rich insert domain in calcium/calmodulin-dependent
  protein kinase kinase for target protein kinases.
  FEBS J. (2022) doi: 10.1111/febs.16467.
(174) Ohtsuka S, Okumura T, Tabuchi Y, Miyagawa T, Kanayama N, Magari M, Hatano N,
  Sakagami H, Suizu F, Ishikawa T, Tokumitsu, H.
  Conformation-Dependent Reversible Interaction of Ca2+/ Calmodulin-Dependent Protein
  Kinase Kinase with an Inhibitor, TIM-063.
  Biochemistry 61 : 545-553 (2022)
(173) Fukumoto Y, Harada Y, Ohtsuka S, Kanayama N, Magari M, Hatano N, Sakagami H,
  Tokumitsu H.
  Oligomerization of Ca2+/calmodulin-dependent protein kinase kinase.
  Biochem. Biophys. Res. Commun. 587:160-165 (2022)
(172) Pakkarato S, Sakagami H, Goto K, Watanabe M, Kondo H, Hipkaeo W, Chomphoo S.
  Localization of phosphatidylinositol phosphate 5 kinase γ phospholipase β3 and
  diacylglycerol kinase ζ in corneal epithelium in comparison with conjunctival epithelium of
  mice.
  Exp. Eye Res. 223: 109205 (2022)

2021年red

画像の説明

(171) Ito A, Fukaya M, Sugawara T, .
  Hara Y, Okamoto H, Yamauchi J,
  Sakagami H.
  Cytohesin-2 mediates group I
  metabotropic glutamate
  receptor-dependent mechanical
  allodynia through the activation
  of ADP ribosylation factor 6 in
  the spinal cord.
  Neurobiol. Dis. 159:105466
  (2021) doi: 10.1016/j.nbd.2021.
  105466.
  サイトヘジン2-Arf6経路の脊髄後角ニューロンにおいて代謝型グルタミン酸受容体依存的な
  中枢感作の制御を介して痛覚感受性に関わることと、サイトヘジン阻害剤による炎症性
  および神経障害性慢性疼痛への効果をマウスレベルで明らかにしました。

(170) Sirisin J, Kamnate A, Polsan Y, Somintara S, Chomphoo S, Sakagami H,
  Kondo H, Hipkaeo W,
  Localization of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) α confined to the
  surface of lipid droplets and adjacent narrow cytoplasm in progesterone-producing cells of
  in situ ovaries of adult mice.
  Acta Histochem. 123: 151794 (2021)(169) Kato Y, Ochiai A, Seki Y, Morimoto T, Oizumi H, Ohbuchi K, Mizoguchi K, Yamamoto M,
  Sakagami H, Miyamoto Y, Yamauchi J. (2021)
  Phospholipase D and phosphatidylinositol-4-phosphate 5-kinase 1 are involved in the
  regulation of oligodendrocyte morphological differentiation.
  Exp Cell Res. 405:112654 (2021)
(168) Nishinarita R, Niwano S, Niwano H, Nakamura H, Saito D, Sato T, Matsuura G, Arakawa
  Y, Kobayashi S, Shirakawa Y, Horiguchi A, Ishizue N, Igarashi T, Yoshizawa T, Oikawa J,
  Hara Y, Katsumura T, Kishihara J, Satoh A, Fukaya H, Sakagami H, Ako J.
  Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model.
  J Am Heart Assoc. 10: e017483 (2021)
(167) Kawarada L, Fukaya M, Saito R, Kassai H, Sakagami H, Aiba A.
  Telencephalon-specific Alkbh1 conditional knockout mice display hippocampal atrophy and
  impaired learning.
  FEBS Lett. 595:1671-1680 (2021)
(166) Murakami M, Murakami AM, Matsuzaki Y, Sawamura D, Ohba T, Miyoshi I, Itagaki S,
  Sakagami H.
  Attenuated β-adrenergic response in calcium/calmodulin-dependent protein kinase IV-knock
  out mice.
  PLoS One 16:e0249932 (2021).
(165) Chomphoo S, Sakagami H, Kondo H, Hipkaeo W.
  Localization of PIP5Kγ selectively in propioceptive peripheral fields and also in sensory
  ganglionic satellite cells as well as neuronal cell membranes and their central terminals.
   J. Anat. 239: 1196-1206 (2021) doi: 10.1111/joa.13491.
(164) Ishibashi Y, Shoji S, Ihara D, Kubo Y, Tanaka T, Tanabe H, Hakamata T, Miyata T, Satou N,
  Sakagami H, Mizuguchi M, Kikuchi K, Fukuchi M, Tsuda M, Takasaki I, Tabuchi A.
  Expression of SOLOIST/MRTFB i4, a novel neuronal isoform of the mouse serum response
  factor coactivator myocardin-related transcription factor-B, negatively regulates dendritic
  complexity in cortical neurons.   
   J. Neurochem. 159: 762-777 (2021) doi: 10.1111/jnc.15122.

2020年red
(163) Fukaya M, Sugawara T, Hara Y, Itakura M, Watanabe M, Sakagami H.
  BRAG2a Mediates mGluR-Dependent AMPA Receptor Internalization at Excitatory
  Postsynapses through the Interaction with PSD-95 and Endophilin 3.
   J. Neurosci. 40(22):4277-4296 (2020) doi: 10.1523/JNEUROSCI.1645-19.2020.

画像の説明

  
BRAG2の新たな結合分子としてEndophilinを見出し、mGluR1/5刺激に伴い海馬ニューロンのシナプス後膜においてEndophilinと複合体と形成し、Arf6を活性化しAMPA受容体のクラスリン依存的エンドサイトーシスを制御することを見出した。mGluR依存的な長期抑圧(LTD)において、BRAG2はエンドサイトーシスの積荷としてのAMPARとエンドサイトーシス制御分子Endophilinとを繋ぐ役割を担うことを明らかにしました。
                                                                  
(162) Ibuchi K, Fukaya M, Shinohara T, Hara Y, Shiroshima T, Sugawara T, Sakagami H.
  The Vps52 Subunit of the GARP and EARP Complexes Is a Novel Arf6-interacting Protein
  That Negatively Regulates Neurite Outgrowth of Hippocampal Neurons.
   Brain Res. 28:146905 (2020) doi: 10.1016/j.brainres.2020.146905.
(161) Moriguchi S, Inagaki R, Yi L, Shibata M, Sakagami H, Fukunaga K.
  Nicotine Rescues depressive-like behaviros via a7-type nicotinic acetylcholine receptor
  activation in CaMKIV null mice.
   Mol. Neurobiol. (2020) doi: 10.1007/s12035-020-02077-z.
(160) Takabatake S, Fukumoto Y, Ohtsuka S, Kanayama N, Magari M, Sakagami H, Hatano N,
  Tokumitsu H.
  Phosphorylation and dephosphorylation of Ca2+/calmodulin-dependent protein kinase
  kinase β at Thr144 in HeLa cells.
   Biochem. Biophys. Res. Commun. 525: 251-257 (2020)
(159) Chomphoo S, Sakagami H, Kondo H, Hipkaeo W.
  Discrete localization patterns of Arf6, and its activators EFA6A and BRAG2, and its effector
  PIP5kinase γ on myofibrils of myotubes and plasma membranes of myoblasts in
  developing skeletal muscles of mice.
  Acta Histochem. 122(3):151513 (2020)

2019年red
(158) Saegusa S, Fukaya M, Kakegawa W, Tanaka M, Katsumata O, Sugawara T, Hara Y,
  Itakura M, Okubo T, Sato T, Yuzaki M, Sakagami M.
  Mice lacking EFA6C/Psd2, a guanine nucleotide exchange factor for Arf6, exhibit lower
  Purkinje cell synaptic density but normal cerebellar motor functions.
  PLoS One14(5) e0216960 (2019)

画像の説明

2005年に小脳プルキンエ細胞に発現するArf6活性化制御因子EFA6Cに対する遺伝子欠損マウスの小脳機能に関する論文で、医学部学生の三枝君が第一著者。EFA6Cの遺伝欠損により、小脳皮質の顆粒細胞の平行線維とプルキンエ細胞間のシナプス密度が低下することを見出した。
                                                                  
(157) Sakai Y, Kassai H, Nakayama H, Fukaya M, Maeda T, Nakao K, Hashimoto K,
  Sakagami H, Kano M, Aiba A.
  Hyperactivation of mTORC1 disrupts cellular homeostasis in cerebellar Purkinje cells.
  Sci. Rep. 9(1): 2799. (2019)
(156) Khrongyut S, Rawangwong A, Pidsaya A, Sakagami H, Kondo H, Hipkaeo W.
  Localization of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) α, β, γ in the three major
  salivary glands in situ of mice and their response to β-adrenoceptor stimulation.
  J. Anatomy 234:502-514 (2019)
(155) Tatsumi Y, Matsumoto N, Iibe N, Watanabe N, Torii T, Sango K, Homma K, Miyamoto Y,
  Sakagami H, Yamauchi J.
  CMT type 2N disease-associated AARS mutant inhibits neurite growth that can be reversed
  by valproic acid.
  Neurosci. Res. 139:69-78 (2019)
(154) Nito R, Kassai H, Sakai Y, Schönherr S, Fukaya M, Schwarzer C, Sakagami H, Nakao K,
  Aiba A, Ferraguti F.
  New features on the expression and trafficking of mGluR1 splice variants exposed by two
  novel mutant mouse lines.
  Front. Mol. Neurosci. 11:439 (2018)
(153) Takabatake S, Ohtsuka S, Sugawara T, Hatano N, Kanayama N, Magari M, Sakagami H,
  Tokumitsu H.
  Regulation of Ca2+/calmodulin-dependent protein kinase kinase β by cAMP signaling.
  Biochim Biophys Acta Gen Subj. 1863: 672-680 (2019)
(152) Kikuchi K, Ihara D, Fukuchi M, Tanabe H, Ishibashi Y, Tsujii J, Tsuda M, Kaneda M,
  Sakagami H, Okuno H, Bito H, Yamazaki Y, Ishikawa M, Tabuchi A.
  Involvement of SRF coactivator MKL2 in BDNF-mediated activation of the synaptic activity-
  responsive element in the Arc gene.
  J Neurochem. 148: 204-218(2019)

2018年red
(151) Moriguchi S, Kita S, Inagaki R, Yabuki Y, Sasaki Y, Ishikawa S, Sakagami H, Iwamoto T,
  Fukunaga K.
  Aberrant Amygdala-Dependent Cued Fear Memory in Na+/Ca2+ Exchanger 1
  Heterozygous Mice.
  Mol Neurobiol. (2018) in press
(150) Naito R, Kassai H, Sakai Y, Schönherr S, Fukaya M, Schwarzer C, Sakagami H, Nakao K,
  Aiba A, Ferraguti F.
  New Features on the Expression and Trafficking of mGluR1 Splice Variants Exposed by
  Two Novel Mutant Mouse Lines.
  Front Mol Neurosci. 11:439 (2018)
(149) Hara Y, Fukaya M, Sugawara T, Sakagami H.
  FIP4/Arfophilin-2 plays overlapping but distinct roles from FIP3/Arfophilin-1 in neuronal
  migration during cortical layer formation.
  Eur J Neurosci. 48:3082-3096 (2018)

画像の説明

2016年にArf6の神経細胞移動の下流効果分子としてFIP-3/Arfophilin-1を見出し報告した(Hara et al., eNeuro 2016)が、今回、Arf6と相互作用する同じclass II FIPファミリーに属するFIP4/Arfophilin-4に着目して、神経細胞移動における機能解析を行い、FIP4/Arfophilin-4が、FIP-3/Arfophilin-1と異なる細胞内小胞輸送経路を介して神経細胞移動を制御することを見出した。                                                                  
(148) Ito A, Fukaya M, Saegusa S, Kobayashi E, Sugawara T, Hara Y, Yamauchi J, Okamoto H,
  Sakagami H.
  Pallidin is a novel interacting protein for cytohesin-2 and regulates the early endosomal
  pathway and dendritic formation in neurons.
  J. Neurochem. 147: 153-177 (2018)

画像の説明

Arf6活性化制御因子Cytohesin-2の新規結合タンパク質として、BLOC-1複合体のサブユニット分子Pallidinを見出し、海馬神経細胞においてCytohesin-2とPallidinとの相互作用が、細胞内小胞輸送を介しての樹状突起形成に関与することを見出した。海馬神経細胞におけるCytohesin-2の細胞内局在に関する免疫電子顕微鏡データが表紙に選ばれた。                                                                  
(147) Chomphoo S, Pakkarato S, Sawatpanich T, Sakagami H, Kondo H, Hipkaeo W.
  Localization of EFA6 (exchange factor for ARF6) isoform D in steroidogenic testicular
  Leydig cells of adult mice.
  Acta Histochem. 120(3):263-268 (2018)
(146) Moriguchi S, Ishizuka T, Yabuki Y, Shioda N, Sasaki Y, Tagashira H, Yawo H, Yeh JZ,
  Sakagami H, Narahashi T, Fukunaga K.
  Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism
  relevant to Alzheimer's disease therapy.
  Mol Psychiatry 23:211-221 (2018)
(145) Urai Y, Yamawaki M, Watanabe N, Seki Y, Morimoto T, Tago K, Homma K, Sakagami H,
  Miyamoto Y, Yamauchi J.
  Pull down assay for GTP-bound form of Sar1a reveals its activation during morphological
  differentiation.
  Biochem Biophys Res Commun. 10:2047-2053 (2018)

2017年red
(144) Tsuneishi R, Matsumoto N, Itaoka M, Urai Y, Kaneko M, Watanabe N, Takashima S, Seki
  Y, Morimoto T, Sakagami H, Miyamoto Y, Yamauchi J.
  Data on the effect of knockout of cytohesin-1 in myelination-related protein kinase signaling.
  Data Brief 15:234-239 (2017) doi: 10.1016/j.dib.2017.09.024.
(143) Kakizaki T, Sakagami H, Sakimura K, Yanagawa Y.
  A glycine transporter 2-Cre knock-in mouse line for glycinergic neuron-specific gene
  manipulation.
  IBRO Reports 3: 9-16 (2017)
(142) Okuda K, Kobayashi S, Fukaya M, Watanabe A, Murakami T, Hagiwawa M, Sato T, Ueno
  H, Ogonuki N, Komano-Inoue S, Manabe H, Yamaguchi M, Ogura A, Asahara H, Sakagami
  H, Mizuguchi M, Manabe T, Tanaka T.
  CDKL5 controls postsynaptic localization of GluN2B-containing NMDA receptors in the
  hippocampus and regulates seizure susceptibility
  Neurobiol. Dis. 106:158-170 (2017)
(141) Katsumata O, Mori M, Sawane Y, Niimura T, Ito A, Okamoto H, Fukaya M, Sakagami H.
  Cellular and subcellular localization of ADP-ribosylation factor 6 in mouse peripheral tissues
  Histochem Cell Biol. 148:577-598 (2017)

画像の説明

これまでArf6抗体による免疫組織学的検出は困難と考えられてきたが、TE(9.0)バッファーを用いたオートクレーブによる抗原賦活化により、見事に抗原性が回復し免疫反応を検出できることを見出し、Arf6の包括的な組織分布と局在を明らかにした。表紙の図は、子宮内膜でのArf6(緑色), E-カドヘリン(青色),オクルディン(赤色)の3重免疫染色により、Arf6が細胞膜側部に豊富に分布し、タイト結合部分でオクルディンと共局在することを示す。                                                                  
(140) Sakagami H, Katsumata O, Hara Y, Sasaoka T, Fukaya M.
  BRAG2a, a guanine nucleotide exchange factor for Arf6, is a component of the dystrophin-
  associated glycoprotein complex at the photoreceptor terminal.
  Invest Ophthalmol Vis Sci. 58:3795-3803 (2017)

画像の説明

筋ジストロフィー症において、骨格筋症状以外に中枢神経症状や網膜電図の異常を示すことが知られているが、その機序は不明である。
本研究では、免疫組織学的及び免疫沈降法を用いた生化学的な解析により、網膜視細胞のリボンシナプスにおいてBRAG2aがジストロフィンと複合体を形成することを示し、網膜でのジストロフィン・糖タンパク質複合体の分子基盤の手がかりを見出した。                                                                  
(139) Tachow A, Thoungseabyoun W, Phuapittayalert L, Petcharat K, Sakagami H.
  Co-localization of endogenous Arf6 and its activator EFA6D in the granular convoluted
  tubule cells of mouse submandibular glands under normal conditions and when stimulated
  by isoproterenol, noradrenaline and carbachol.
  Arch Oral Biol. 82:153-159 (2017)
(138) Nakamori T, Kato T, Sakagami H, Tanaka K, Ohki-Hamazaki H.
  Regulation of visual Wulst cell responsiveness by imprinting causes stimulus-specific
  activation of rostral cells.
  Sci Rep. 7:42927(2017)

2016年red
(137) Kusano R, Fujita K, Shinoda Y, Nagaura Y, Kiyonari H, Abe T, Watanabe T, Matsui Y,
  Fukaya M, Sakagami H, Sato T, Funahashi JI, Ohnishi M, Tamura S, Kobayashi T.
  Targeted disruption of the mouse protein phosphatase ppm1l gene leads to structural
  abnormalities in the brain.
  FEBS Lett. 590:3606-3615 (2016)
(136) Hara Y, Fukaya M, Hayashi K, Kawauchi T, Nakajuma K, Ohata S, Sakagami H.
  ADP ribosylation factor 6 regulates neuronal migration in the developing cerebral cortex
  through FIP3/Arfophilin-1-dependent endosomal trafficking of N-cadherin.
  eNeuro 3(4). pii: ENEURO.0148-16.2016 (2016)
大脳皮質層形成過程において、Arf6がFIP3/Arfophilin-1との相互作用を介したN-カドヘリンの小胞輸送により、中間層での多極性移動に関与することを明らかにした。
画像の説明
(135) Sakagami H, Hara Y, Fukaya M.
  Interaction of serologically defined colon cancer antigen-3 with Arf6 and its predominant
  expression in the mouse testis.
  Biochem Biophys Res Commun. 477: 868-873 (2016)
酵母ツーハイブリット法により大腸癌血清抗原として発見されていたSDCCAG3がGTP結合型Arf6を特異的に結合すること、Arf6との結合がSDCCAG3のの細胞質分裂時の中央体への局在に重要であることを明らかにした。
画像の説明
(134) Chomphoo S, Mothong W, Sawatpanich T, Kanla P, Sakagami H, Kondo H, Hipkaeo W.
  Ultrastructural localization of endogenous exchange factor for ARF6 in adrenocortical cells
  in situ of mice.
  Acta Histochem Cytochem. 49:83-87 (2016)
(133) Tanahashi H, Tian QB, Hara Y, Sakagami H, Endo S, Suzuki T.
  Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the
  pathways of amniotic fluid clearance.
  Sci. Rep. 6: 20241 (2016)
(132) Jusuf AA, Sakagami H, Kikkawa S, Terashima T.
  Expression of β subunit of Ca2+/calmodulin-dependent protein kinase I in the developing
  rat retina.
  Kobe J. Med. Sic. 61:E115-123 (2016)
(131) Fukaya M, Ohata S, Hara Y, Tamaki H, Sakagami H.
  Distinct subcellular localization of alternative splicing variants of EFA6D, a guanine
  nucleotide exchange factor for Arf6, in the mouse brain.
  J. Comp. Neurol. 524:2531-2552 (2016) 

画像の説明

Arf6特異的活性化制御因子EFA6Dのアイソフォームに関するN末とC末領域のスプライスに違いに基づいた名称と分類を提唱した。また、神経系において豊富に発現するArfGEF活性を有するEFA6D1b/cは、EFA6AやEFA6Cとは異なり、軸索に豊富に局在することを明らかにし、EFA6ファミリー分子による多様な細胞内局在がArf6の多彩な神経機能を可能にしている解剖学的な証拠を提示した。                                                                    
2015年red
(130) Amano H, Kato S, Ito Y, Eshima K, Ogawa F, Takahashi R, Sekiguchi K, Tamaki H,
  Sakagami H, Shibuya M, Majima M.
  The Role of Vascular Endothelial Growth Factor Receptor-1 Signaling in the Recovery from
  Ischemia.
  PLoS One. 10:e0131445 (2015)
(129) Amano H, Ito Y, Exhima K, Kato S, Ogawa F, Hosono K, Obata K, Tamaki H, Sakagami H,
  Shibuya M, Narumiya S, Majima M.
  Thromboxane A2 induces blood flow recovery via platelet adhesion to ischaemic regions.
  Cardiovasc. Res.107:509-521 (2015)
(128) Shirai Y, Watanabe M, Sakagami H, Suzuki T.
  Novel splice variants in the 5’UTR of Gtf2i expressed in the rat brain: alternative 5’ETR
  and differential expression in the neuronal dendrites.
  J. Neurochem.134:578-589 (2015)
(127) Torii T, Miyamoto Y, Yamamoto M, Ohbuchi K, Tsumura H, Kawahara K, Tanoue A,
  Sakagami H, Yamauchi J.
  Data supporting Arf6 regulation of Schwann cell differentiation and myelination.
  Data Brief. 5:388-395 (2015).
(126) Torii T, Miyamoto Y, Yamamoto M, Ohbuchi K, Tsumura H, Kawahara K, Tanoue A,
  Sakagami H, Yamauchi J.
  Arf6 mediates Schwann cell differentiation and myelination.
  Biochem Biophys Res Commun.465:450-457 (2015)
(125) Torii T, Ohno N, Miyamoto Y, Kawahara K, Saitoh Y, Nakamura K, Takashima S,
  Sakagami H, Tanoue A, Yamauchi
  Arf6 guanine-nucleotide exchange factor cytohesin-2 regulates myelination in nerves.
  Biochem Biophys Res Commun. 2015 May 8;460(3):819-825.
(124) Moriguchi S, Sakagami H, Sasaki Y, Izumi H, Yabuki Y, Zhang C, Fukunaga K.
  Stimulation of sigma-1 receptor ameliorates depressive-like behaviors in CaMKIV null mice.
  Mol. Neurobiol. 52: 1210-1222 (2015)
(123) Nakamori T, Sata K, Kinoshita M, Kanamatsu T, Sakagami H, Tanaka K,Ohki-Hamazaki H.
  Positive feedback in activation of NR2B-containing NMDA receptors is the initial step of
  visual imprinting, a model of juvenile learning.
  J. Neurochem. 132:110-123 (2015)

2014年red
(122) Akiyama M, Hasegawa H, Hongu T, Frohman MA, Harada A, Sakagami H, Kanaho Y.
  Trans-regulation of oligodendrocyte myelination by neurons through
  small GTPase Arf6-regulated secretion of fibroblast growth factor-2.
  Nature Commun. 5: 4744 (2014)
(121) Sakagami H, Katsumata O, Hara Y, Tamaki H, Fukaya M.
  Preferantial localization of type I phosphatidylinositol 4-phosphate 5-kinase γ at the
  periactive zone of mouse photoreceptor ribbon synapses.
   Brain Res. 1586:23-33 (2014)
Arf6の下流効果分子のホスファチジルイノシトール4-2リン酸5キナーゼγ (PIP5KIγ)が、網膜光感受細胞のリボンシナプスにおいてエンドサイトーシス・ゾーンに特異的に局在することを免疫組織学的に明らかにした。画像の説明
(120) Zhao L, Sakagami H, Suzuki T.
  Detergent-dependent separation of postsynaptic density membrane rafts and other
  subsynaptic structures from the synaptic plasma membrane of rat forebrain.
   J. Neurochem. 13:147-162 (2014)
(119) Yazaki Y, Hara Y, Tamaki H, Fukaya M, Sakagami H.
  Endosomal localization of FIP3/Arfophilin-1 and its involvement in dendritic formation of
  mouse hippocampal neurons.
   Brain Res. 1557:55-65 (2014)
(118) Fukaya M, Fukushima D, Hara Y, Sakagami H.
  EFA6A, a gunanine nucleotide exchange factor for Arf6, interacts with sorting nexin-1 and
  regulates neurite outgrowth.
   J. Neurochem. 129:21-36 (2014)
  Arf6特異的活性化制御因子EFA6Aの神経細胞の微細構造における局在に関する免疫電顕解
  析の結果、EFA6Aが神経細胞の樹状突起や棘突起の小胞やシナプス後肥厚部に局在するこ
  とを初めて明らかにした。
  また、EFA6Aが、エンドゾームでの動態に関わるsorting nexin-1(SNX1)と棘突起の小胞膜
  やシナプス後肥厚部において複合体を形成することを明らかにした。さらにNeuro2a細胞
  において、EFA6AとSNX1との共発現により神経突起の形成が促進することより、神経突
  起形成におけるEFA6A-Arf6経路の新たな分子機構を示した。
画像の説明
(117) Moriguchi S, Tagashira H, Sasaki Y, Yeh JZ, Sakagami H, Narahashi T, Fukunaga K.
  CaMKII activity is essential for improvement of memory-related behavior by chronic
  rivastigmine treatment.
   J. Neurochem. 128:927-937 (2014)
2013年red
(116) Hara Y, Fukaya M, Tamaki H, Sakagami H.
  Type I phosphatidylinositol 4-phosphate 5-kinase γ is required for neuronal migration in
  the mouse developing cerebral cortex.
  Eur. J. Neurosci. 38: 2659-2671 (2013)

画像の説明

ホスファチジルイノシトール4,5-2リン酸の神経系での主要な合成酵素であるホスファチジルイノシトール4-2リン酸5キナーゼγ (PIP5KIγ)が大脳皮質の層形成過程において、神経細胞の移動に関与することを子宮内電気穿孔法を用いて明らかにした。また、その分子機序として、PIP5KIγをノックダウンした移動神経細胞においてインテグリンの細胞内アダプター蛋白質 talinの細胞膜への集積に異常があることを示した。
                                                                     
(115) Ueda T, Hanai A, Takei T, Kubo K, Ohgi M, Sakagami H, Takahashi S, Shin HW,
  Nakayama K.
  EFA6 activates Arf6 and participates in its targeting to the Flemming body during
  cytokinesis.
  FEBS Lett. 583:1617-1623 (2013)
(114) Song N, Nakagawa S, Izumi T, Toda H, Kato A, Boku S, Inoue T, Sakagami H, Li X,
  Koyama T.
  Involvement of CaMKIV in neurogenic effect with chronic fluoxetine treatment.
  Int J Neuropsychopharmacol. 16(4):803-812 (2013)
  *CaMKIVが抗うつ薬フルオキセチンによる海馬歯状回における神経細胞新生に関与する
  こと、フルオキセチンによる転写因子CREB活性化に対するリン酸化酵素として機能する
  ことをCaMKIVノックアウトマウスを用いて示した。
(113) Sakagami H, Katsumata O, Hara Y, Tamaki H, Watanabe M, Harvey RJ, Fukaya M.
  Distinct synaptic localization patterns of brefeldin A-resistant guanine nucleotide
  exchange factors BRAG2 and BRAG3 in the mouse retina.
  J. Comp. Neurol. 521: 860-876, 2013.
  *Arf6活性化制御因子BRAGファミリー分子の網膜における免疫電顕による局在解析
   画像の説明

2012年red
(112) Tamaki H, Sanda M, Katsumata O, Hara Y, Fukaya M, Sakagami H.
  Pilt is a coiled-coil domain-containing protein that localizes at the trans-Golgi complex and
  regulates its structure.
  FEBS Lett. 586:3064-3070, 2012.
  *Arf6の新たな結合タンパク質としてのPiltの同定。Piltはトランスゴルジ複合体や
  エンドゾームに局在し、ゴルジ装置の構造維持に必要であることを示した。
(111) Pokorski M, Sakagami H, Okada Y.
  Calcium/calmodulin-dependent protein kinases in the carotid body:
  an immunohistochemical study.
  Springerplus 1:16 (2012).
(110) Pan YW, Zou J, Wang W, Sakagami H, Garelick MG, Abel G, Kuo CT, Storm DR, Xia Z.
  Inducible and Conditional Deletion of Extracellular Signal-regulated Kinase 5 Disrupts
  Adult Hippocampal Neurogenesis.
   J Biol Chem. 287(28):23306-23317, 2012.
(109) Nakata Y, Yasuda T, Fukaya M, Yamamori S, Itakura M, Nihira T, Hayakawa H,
  Kawanami A, Kataoka M, Nagai M, Sakagami H, Takahashi M, Mizuno Y, Mochizuki H.
  Accumulation of α-synuclein triggered by presynaptic dysfunction.
  J. Neurosci. 32:17186-17196, 2012.
(108) Minamino T, Ito Y, Ohkubo H, Hosono K, Suzuki T, Sato T, Ae T, Shibuya A,
  Sakagami H, Narumiya S, Koizumi W, Majima M.
  Thromboxane A(2) receptor signaling promotes liver tissue repair after toxic injury
  through the enhancement of macrophage recruitment.
  Toxicol Appl Pharmacol. 259:104-114, 2012.
(107) Katoh H, Yamashita K, Waraya M, Margalit O, Ooki A, Tamaki H, Sakagami H,
  Kokubo K, Sidransky D, Watanabe M.
  Epigenetic silencing of HOPX promotes cancer progression in colorectal cancer.
  Neoplasia 14:559-571, 2012.

2011年red
(106) Nishimaru H, Sakagami H, Kakizaki M, Yanagawa Y.
  Locomotor-related activity of GABAergic interneurons localized in the ventrolateral region
  in the isolated spinal cord of neonatal mice.
   J Neurophysiol. 106(4):1782-1792, 2011.
(105) Yamamori S, Itakura M, Sugaya D, Katsumata O, Sakagami H, Takahashi M.
  Differential expression of SNAP-25 family proteins in the mouse brain.
  J. Comp. Neurol. 519:916-932, 2011
(104) Isono M, Suzuki T, Hosono K, Hayashi I, Sakagami H, Uematsu S, Akira S,
  DeClerck YA, Okamoto H, Majima M.
  Microsomal prostaglandin E synthase-1 enhances bone
  cancer growth and bone cancer-related pain behaviors in mice.
  Life Sci. 88(15-16):693-700, 2011.
(103) Hosono K, Suzuki T, Tamaki H, Sakagami H, Hayashi I, Narumiya S, Alitalo K, Majima M
  Roles of prostaglandin E2-EP3/EP4 receptor signaling in the enhancement of
  lymphangiogenesis during fibroblast growth factor-2-induced granulation formation.
  Arterioscler Thromb Vasc Biol. 31(5):1049-1058, 2011.
(102) Kato T, Ito Y, Hosono K, Suzuki T, Tamaki H, Minamino T, Kato S,
  Sakagami H, Shibuya M, Majima M. Vascular endothelial growth factor receptor-1
  signaling promotes liver repair through restoration of liver microvasculature after
  acetaminophen hepatotoxicity.
  Toxicol Sci. 120:218-229, 2011.
(101) Fukaya M, Kamata A, Hara Y, Tamaki H, Katsumata O, Ito N, Takeda S, Hata Y,
  Suzuki T, Watanabe M, Harvey RJ, Sakagami H.
  SynArfGEF is a guanine nucleotide exchage factor for Arf6 and localizes preferentially
  at post-synaptic specialization of inhibitory synapases.
  J. Neurochem. 116:1122-1137, 2011.
(100) Takaso M, Nakazawa T, Imura T, Fukushima K, Ueno M, Saito W, Shintani R,
  Sakagami H, Takahashi K, Yamazaki M, Ohtori S, Kotani T.
  Less invasive and less technically demanding decompressive procedure for lumbar
  spinal stenosis – appropriate for general orthopaedic surgeons?
  International Orthopaedics 35: 67-73, 2011.

2010年red
(99) Sakai Y, Aminaka M, Takata A, Kudou Y, Yamauchi H, Aizawa Y, Sakagami H.
  Oxidative stress in mature rat testis and its developmental changes.
  Dev. Growth Differ. 52:657-663, 2010.
(98) Tokumitsu H, Hatano N, Tsuchiya M, Yurimoto S, Fujimoto T, Ohara N, Kobayashi R,
  Sakagami H.
  Identification and characterization of PRG-1 as a neuronal calmodulin-binding protein.
  Biochem J. 43:81-91, 2010.
(97) Ishikawa M, Nishijima N, Shiota J, Sakagami H, Tsuchida K, Mizukoshi M, Fukuchi M,
  Tsuda M, Tabuchi A.
   Involvement of the serum response factor coactivator megakaryoblastic leukemia
   (MKL) in the activin-regulated dendritic complexity of rat cortical neurons.
  J Biol Chem. 285:32734-32743, 2010.
(96) Théard D, Labarrade F, Partisani M, Milanini J, Sakagami H, Fon EA, Wood SA,
  Franco M, Luton F
  USP9x-mediated deubiquitination of EFA6 regulates de novo tight junction assembly.
  EMBO J 29:1499-1509, 2010.
(95) Takaso M, Nakazawa T, Imura T, Okada T, Fukushima K, Ueno M, Takahira N,
  Takahashi K, Yamazaki M, Ohtori S, Okamoto H, Okutomi T, Okamato M, Masaki T,
  Uchinuma E, Sakagami H
   Surgical management of severe scoliosis with high risk pulmonary dysfunction in
  Duchene muscular dystrophy: patient function, quality of life and satisfaction.
  International Orthopaedics 34: 695-702, 2010.
(94) Takao K, Tanda K, Nakamura K, Kasahara J, Nakao K, Katsuki M, Nakanishi K,
  Yamasaki N, Toyama K, Adachi M, Umeda M, Araki T, Fukunaga K, Kondo H,
  Sakagami H, Miyakawa T.
  Comprehensive behavioral analysis of calcium/calmodulin-dependent protein kinase IV
  knockout mice.
  PLoS ONE e9460, 2010.
(93) Sanda M, Ohara N, Kamata A, Hara Y, Tamaki H, Sukegawa J, Yanagisawa T,
  Fukunaga K, Kondo H, Sakagami H.
  Vezatin, a potential target for ADP-ribosylation factor 6, regulates the dendritic formation
  of hippocampal neurons.
  Neurosci. Res. 67(2):126-136, 2010.
(92) Kubo H, Hosono K, Suzuki T, Ogawa Y, Kato H, Kamata H, Ito Y, Amano H, Kato T,
  Sakagami H, Hayashi I, Sugimoto Y, Narumiya S, Watanabe M, Majima M.
  Host prostaglandin EP3 receptor signaling relevant to tumor-associated
  lymphangiogenesis.
  Biomed Pharmacother. 64:101-106, 2010.
(91) Katoh H, Hosono K, Ito Y, Suzuki T, Ogawa Y, Kubo H, Kamata H, Mishima T, Tamaki H,
  Sakagami H, Sugimoto Y, Narumiya S, Watanabe M, Majima M.
  COX-2 and Prostaglandin EP3/EP4 Signaling Regulate the Tumor Stromal Proangiogenic
  Microenvironment via CXCL12-CXCR4 Chemokine Systems.
  Am J Pathol. 176:1469-1483, 2010.
(90) Kato S, Amano H, Ito Y, Eshima K, Aoyama N, Tamaki H, Sakagami H, Satoh Y,
  Izumi T, Majima M.
  Effect of erythropoietin on angiogenesis with the increased adhesion of platelets
  to the microvessels in the hind-limb ischemia model in mice.
  J Pharmacol Sci. 112(2):167-175, 2010.

2009年red
(89) Katsumata O, Ohara N, Tamaki H, Naganuma H, Watanabe M, Sakagami H
  IQ-ArfGEF/BRAG1 is associated with synaptic ribbons in the mouse retina.
  Eur. J. Neurosci. 30:1509-1516, 2009
(88) Wang Y, Kakizaki T, Sakagami H, Saito K, Ebihara S, Kato M,
  Hirobayashi M, Saito Y, Furuya N, Yanagawa Y
  Fluorescent labeling of both GABAergic and glycinergic neurons in VGAT-Venus
  transgenic mouse, Neuroscience 164: 1031-1043, 2009.
(87) Yamagata Y, Kobayashi S, Umeda T, Inoue A, Sakagami H, Fukaya M, Watanabe M,
  Hatanaka N, Totsuka M, Yagi T, Obata K, Imoto K, Yanagawa Y, Manabe T, Okabe S
  Kinase-dead knock-in mouse reveals an essential role of kinase activity of
  Ca2+/calmodulin-dependent protein kinase IIalpha in dendritic spine enlargement,
  long-term potentiation, and learning.
  J Neurosci. 29:7607-18, 2009.
(86) Suzuki R, Saino-Saito S, Sakagami H, Toshimori K, Abe H, Kondo H
  Localization of EFA6A, a guanine nucleotide exchange factor for ARF6, in spermatogenic
  cells of testes of adult mice. J Mol Histol. 40:77-80, 2009.
(85) Sanda M, Kamata A, Katsumata O, Fukunaga K, Watanabe M, Kondo H, Sakagami H
  The postsynaptic density protein, IQ-ArfGEF/BRAG1, can interact with IRSp53 through
  its proline-rich sequence.
  Brain Res.1251:7-15, 2009.

2008年red
(84) Moon II Soo, Sakagami H, Nakayama J, Suzuki T
  Differential distribution of synGAP alpha1 and beta isoforms in rat neurons.
  Brain Res. 1241:62-75, 2008.
(83) Katsumata O, Honma T, Sanda M, Kamata A, Takeda S, Kondo H, Sakagami H
  Predominant localization of EFA6A, a guanine nucleotide exchange factor for ARF6, at
  the perisynaptic photoreceptor processes.
  Brain Res.1234:1244-9,2008.
(82) Yamamoto N, Kaneko I, Motohashi K, Sakagami H, Adachi Y, Tokuda N, Sawada T,
  Furukawa H, Ueyama Y, Fukunaga K, Ono M, Kondo H, Owada Y.
  Fatty acid-binding protein regulates LPS-induced TNF-alpha production in mast cells.
  Prostaglandins Leukot Essent Fatty Acids. 79:21-26, 2008
(81) Maeda K, Haraguchi M, Kuramasu A, Sato T, Ariake K, Sakagami H, Kondo H, Yanai K,
  Fukunaga K, Yanagisawa T,and Sukegawa J
  CLIC4 interacts with histamine H3 receptor and enhances the receptor cell
  surface expression.
  Biochem Biophys Res Commun. 369: 603-608, 2008.
(80) Sakagami H
   The EFA6 family: guanine nucleotide exchange factors for ADP ribosylation factor 6 at
  neuronal synapses.
  Tohoku J. Exp. Med. 214:191-198, 2008
(79) Sakagami H, Sanda M, Fukaya M, Miyazaki T, Sukegawa J, Yanagasawa T, Suzuki T,
  Fukunaga K, Watanabe M, Kondo H.
  IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with
  PSD-95 at postsynaptic density of excitatory synapses.
  Neurosci Res. 60:199-212, 2008
(78) Nakamura K, Ichise H, Nakao K, Hatta T, Otani H, Sakagami H, Kondo H and Katsuki M.
  Partial functional overlap of the three ras genes in mouse embryonic development.
  Oncogene. 27: 2961-2968, 2008

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