Super-resolution imaging of synaptic proteins regulated with ubiquitin ligase SCRAPPER

• Project/Area Number: 26460388
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Yao Ikuko 浜松医科大学, 光尖端医学教育研究センター, 准教授 (60399681)
• Project Period (FY): 2014-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: シナプス / 蛋白質 / 神経可塑性 / ユビキチン / SCRAPPER / 質量分析 / イメージング / 老化 / 超解像

Outline of Final Research Achievements

Dysfunction of the ubiquitination occurs in many neurodegenerative diseases, and neurotransmitter release abnormalities are also involved in many neurological diseases. We tried to understand integratively the regulation of cell and individual function by protein degradation through ubiquitin ligase SCRAPPER which we previously identified. In this study, we found that the amounts of some kinds of proteins were significantly altered in the knockout mouse brain. Moreover, it has become clear that behaviors of several neurotransmitters have changed in the multiple areas of the knockout mouse brain. These alterations may have deep relationship with the roles of SCRAPPER in neural tissue such as neurotransmitter release control, neural plasticity, and fear / anxiety-like behavior.

Academic Significance and Societal Importance of the Research Achievements

本研究はユビキチンプロテアソーム系による神経シナプス脱構築および神経伝達制御の分子機構解明を目指すものである。SCRAPPER依存的なユビキチンプロテアソーム系分解が調節するシナプス関連分子の挙動を明らかにすることは、シナプス伝達の場におけるユビキチン化の時空間的な詳細の解明につながり、ひいては神経難病の医化学的病態理解が進むことが期待される。

Research Products

• [Int'l Joint Research] トロント大学(カナダ)
• [Int'l Joint Research] トロント大学(カナダ)
• [Journal Article] N-3 fatty acids modulate repeated stress-evoked pain chronicity (2019)
  • Author(s): 1.Aizawa F, Sato S, Yamazaki F, Yao I, Yamashita T, Nakamoto K, Kasuya F, Setou M, Tokuyama S
  • Journal Title: Brain Res Volume: 1714 Pages: 218-226
  • DOI: 10.1016/j.brainres.2019.03.001
  • Peer Reviewed
• [Journal Article] Imaging mass spectrometry reveals sodium lauryl sulfate-induced changes in skin lipoquality, principally affecting sphingomyelin (2019)
  • Author(s): Yusuke Saito、Fumihiro Eto、Shiro Takei、Ikuko Yao、Mitsutoshi Setou
  • Journal Title: Medical Mass Spectrometry Volume: 3 Pages: 1-8
  • NAID: 130007897976
  • Peer Reviewed / Open Access
• [Journal Article] Lysophosphatidic acid precursor levels decrease and an arachidonic acid-containing phosphatidylcholine level increases in the dorsal root ganglion of mice after peripheral nerve injury (2018)
  • Author(s): Mihara Yuki、Horikawa Makoto、Sato Shumpei、Eto Fumihiro、Hanada Mitsuru、Banno Tomohiro、Arima Hideyuki、Ushirozako Hiroki、Yamada Tomohiro、Xu Dongmin、Okamoto Ayako、Yamazaki Fumiyoshi、Takei Shiro、Omura Takao、Yao Ikuko、Matsuyama Yukihiro、Setou Mitsutoshi
  • Journal Title: Neuroscience Letters Volume: 698 Pages: 69-75
  • DOI: 10.1016/j.neulet.2018.12.035
  • Peer Reviewed / Open Access
• [Journal Article] Visualization of local phosphatidylcholine synthesis within hippocampal neurons using a compartmentalized culture system and imaging mass spectrometry (2018)
  • Author(s): Sugiyama Eiji、Yao Ikuko、Setou Mitsutoshi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 495 Issue: 1 Pages: 1048-1054
  • DOI: 10.1016/j.bbrc.2017.11.108
  • Peer Reviewed / Open Access
• [Journal Article] Distinct spatial localization of three types of phosphatidyl choline in rat buccal mucosa identified by matrix-assisted laser desorption/ionization imaging mass spectrometry (2017)
  • Author(s): Miyagi M, Fukano H, Atsumi R, Suzuki H, Setou M, Yao I
  • Journal Title: Medical Mass Spectrometry Volume: 1 Issue: 1 Pages: 2-9
  • DOI: 10.24508/mms.2017.06.002
  • NAID: 130007897667
  • ISSN: 2432-7441, 2432-745X
  • Year and Date: 2017-06-25
  • Peer Reviewed / Open Access
• [Journal Article] SCRAPPER Selectively Contributes to Spontaneous Release and Presynaptic Long-Term Potentiation in the Anterior Cingulate Cortex (2017)
  • Author(s): Koga Kohei、Yao Ikuko、Setou Mitsutoshi、Zhuo Min
  • Journal Title: The Journal of Neuroscience Volume: 37 Issue: 14 Pages: 3887-3895
  • DOI: 10.1523/jneurosci.0023-16.2017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sulfatide species with various fatty acid chains in oligodendrocytes at different developmental stages determined by imaging mass spectrometry (2017)
  • Author(s): Yukie Hirahara, Taketoshi Wakabayashi, Tetsuji Mori, Taro Koike, Ikuko Yao, Masayuki Tsuda , Koichi Honke, Hitoshi Gotoh, Katsuhiko Ono, Hisao Yamada.
  • Journal Title: Journal of Neurochemistry Volume: 140 Issue: 3 Pages: 435-450
  • DOI: 10.1111/jnc.13897
  • NAID: 120006778373
  • Peer Reviewed
• [Journal Article] Involvement of Brain-Enriched Guanylate Kinase-Associated Protein (BEGAIN) in Chronic Pain after Peripheral Nerve Injury. (2016)
  • Author(s): Katano T, Fukuda M, Furue H, Yamazaki M, Abe M, Watanabe M, Nishida K, Yao I, Yamada A, Hata Y, Okumura N, Nakazawa T, Yamamoto T, Sakimura K, Takao T, Ito S.
  • Journal Title: eNeuro. Volume: 3 Issue: 5 Pages: 0110-16
  • DOI: 10.1523/eneuro.0110-16.2016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Doublet 7 shortening, doublet 5-preferential poly-Glu reduction, and beating stall of sperm flagella in Ttll9-/- mice. (2016)
  • Author(s): Konno A, Ikegami K, Konishi Y, Yang HJ, Abe M, Yamazaki M, Sakimura K, Yao I, Shiba K, Inaba K, Setou M.
  • Journal Title: J Cell Sci. Volume: 129 Issue: 14 Pages: 2757-2766
  • DOI: 10.1242/jcs.185983
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Microscopic visualization of testosterone in mouse testis by use of imaging mass spectrometry. (2016)
  • Author(s): Shimma, S., Kumada, H-O., Taniguchi, H., Konno, A., Yao, I., Furuta, K., Matsuda, T. and Ito, S.
  • Journal Title: Analytical and bioanalytical chemistry Volume: 408 Issue: 27 Pages: 7607-7615
  • DOI: 10.1007/s00216-016-9594-9
  • Peer Reviewed
• [Journal Article] Expression of hOvol2 in the XY body of human spermatocytes (2016)
  • Author(s): Taniguchi, Hisanori; Katano, Tayo; Nishida, Kazuhiko; Yao, Ikuko; Morimoto, Yoshiharu; Matsuda, Tadashi; Ito, Seiji
  • Journal Title: Andrologia Volume: 48 Issue: 1 Pages: e12599-e12599
  • DOI: 10.1111/and.12599
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Microscopic visualization of testosterone in mouse testis by use of imaging mass spectrometry (2016)
  • Author(s): Shuichi Shimma, Henri-Obadja Kumada, Hisanori Taniguchi, Alu Konno, Ikuko Yao, Kyoji Furuta, Tadashi Matsuda, Seiji Ito
  • Journal Title: Anal Bioanal Chem Volume: 408
  • Peer Reviewed
• [Journal Article] アセチルコリンの質量分析イメージング (2016)
  • Author(s): 矢尾育子
  • Journal Title: Journal of the Mass Spectrometry Society of Japan Volume: 64 Pages: 31-34
  • NAID: 130005125537
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Decreased level of phosphatidylcholine (16:0/20:4) in multiple myeloma cells compared to plasma cells: A single-cell MALDI-IMS approach. (2015)
  • Author(s): Hossen A, Nagata Y, Waki M, Ide Y, Takei S, Fukano H, Romero-Perez GA, Tajima S, Yao I, Ohnishi K,Setou M.
  • Journal Title: Anal Bioanal Chem Volume: 407 Issue: 18 Pages: 5273-80
  • DOI: 10.1007/s00216-015-8741-z
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Alisa G. Woods and Costel C. Darie (Eds.): Advancements of mass spectrometry in biomedical research. (2015)
  • Author(s): Setou M, Yao I: Alisa G
  • Journal Title: Anal Bioanal Chem Volume: 407 Issue: 9-10 Pages: 1283-1284
  • DOI: 10.1007/s10337-015-2888-9
  • Peer Reviewed
• [Journal Article] DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease. (2014)
  • Author(s): Yuki D, Sugiura Y, Zaima N, Akatsu H, Takei S, Yao I, Maesako M, Kinoshita A, Yamamoto T, Kon R, Sugiyama K, Setou M.
  • Journal Title: Sci Rep Volume: - Issue: 1 Pages: 7130-7130
  • DOI: 10.1038/srep07130
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 質量分析イメージングの最新動向 －質量顕微鏡法について (2014)
  • Author(s): 武井史郎，矢尾育子
  • Journal Title: インナービジョン Volume: 29 Pages: 53-57
  • Acknowledgement Compliant
• [Presentation] 質量分析イメージングで可視化されたScrapperノックアウトマウス脳における神経伝達変化 (2018)
  • Author(s): 衞藤史博、松田孟士、瀬藤光利、矢尾育子
  • Organizer: 第41回日本神経科学大会
• [Presentation] 質量分析イメージングを用いたAPP/PS1アルツハイマー病モデルマウス脳組織におけるアセチルコリン分泌減少の可視化 (2018)
  • Author(s): 松田 孟士、深野 華、久恒 辰博、矢尾 育子
  • Organizer: 第41回日本神経科学大会
• [Presentation] The breakdown of free fatty acids-GPR40/FFAR1 signaling in the brain induce development of chronic pain after social defeat stress in mice (2018)
  • Author(s): Aizawa Fuka、Yao Ikuko、Sato Shumpei、Yamazaki Fumiyoshi、Yamashita Takuya、Nakamoto Kazuo、Hirasawa Akira、Kurihara Takashi、Kasuya Fumiyo、Miyata Atsuo、Setou Mitsutoshi、Tokuyama Shogo
  • Organizer: the 50th annual meeting of the Society for Neuroscience
  • Int'l Joint Research
• [Presentation] Imaging mass spectrometry revealed the alteration of amine neurotransmitters in Scrapper-knockout mice brain (2018)
  • Author(s): Eto Fumihiro、Matsuda Takeshi、Setou Mitsutoshi、Yao Ikuko
  • Organizer: the 50th annual meeting of the Society for Neuroscience
  • Int'l Joint Research
• [Presentation] A manifold learning approach to imaging mass spectrometry analysis in mice brain (2018)
  • Author(s): Suetani Hiromichi、Eto Fumihiro、Yao Ikuko
  • Organizer: the 50th annual meeting of the Society for Neuroscience
  • Int'l Joint Research
• [Presentation] Analysis of rivastigmine distribution in the brain by imaging mass spectrometry (2017)
  • Author(s): Matsuda T, Fukano H, Eto F, Yao I
  • Organizer: 第36回日本認知症学会学術集会
• [Presentation] Brain amine neurotransmitters are comprehensively visualized by matrix-free laser desorption/ionization imaging mass spectrometry using a unique photocleavable derivatizing agent (2017)
  • Author(s): Matsuda T, Fukano H, Waki M, Takei S, Eto F, Setou M, Maki T, Yao I
  • Organizer: the 47th annual meeting of the Society for Neuroscience
  • Int'l Joint Research
• [Presentation] Alteration of amine neurotransmitters in Scrapper-knockout mice brain visualized by imaging mass spectrometry (2017)
  • Author(s): Eto F, Matsuda T, Setou M, Yao I
  • Organizer: the 47th annual meeting of the Society for Neuroscience
  • Int'l Joint Research
• [Presentation] MALDI-IMSを用いたScrapperノックアウトマウス脳組織における神経伝達物質局在分布の可視化 (2017)
  • Author(s): 衞藤史博、松田孟士、瀬藤光利、矢尾育子
  • Organizer: 第42回日本医用マススペクトル学会年会
• [Presentation] MALDI-IMSを用いたマウス肺組織におけるアセチルコリン局在分布の可視化 (2017)
  • Author(s): 松田孟士、矢尾育子
  • Organizer: 第42回日本医用マススペクトル学会年会
• [Presentation] 光開裂分子を用いたアミノ酸神経伝達物質の質量分析イメージング (2017)
  • Author(s): 矢尾育子、深野華、脇紀彦、瀬藤光利、真木俊英
  • Organizer: 第40回日本神経科学大会
• [Presentation] 記憶障害を有するAβPPswe/PSEN1dE9アルツハイマー病モデルマウス脳組織におけるアセチルコリンの質量分析イメージング (2017)
  • Author(s): 松田孟士、久恒辰博、矢尾育子
  • Organizer: 第40回日本神経科学大会
• [Presentation] 光開裂分子を用いた神経伝達物質のイメージング (2017)
  • Author(s): 深野華、脇紀彦、武井史郎、瀬藤光利、真木俊英、矢尾育子
  • Organizer: 第65回質量分析総合討論会
• [Presentation] 超解像イメージングによるシナプス伝達制御機構の解析 (2017)
  • Author(s): 矢尾育子
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Invited
• [Presentation] 質量顕微鏡法による神経疾患モデル動物解析に向けて (2016)
  • Author(s): 矢尾育子
  • Organizer: 第121回日本解剖学会総会・全国学術集会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] ユビキチンリガーゼ SCRAPPERによるシナプス可塑性の調節 (2016)
  • Author(s): 矢尾育子
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター （北海道札幌市）
  • Year and Date: 2016-03-22
  • Invited
• [Presentation] Mass spectrometry imaging for transitional condition of a drug to the mouse brain (2016)
  • Author(s): Yao I
  • Organizer: 第1回国際マスイメージングセンターミーティング
  • Place of Presentation: 浜松医科大学（静岡県浜松市）
  • Int'l Joint Research / Invited
• [Presentation] 質量分析イメージングの実際 (2015)
  • Author(s): 矢尾育子
  • Organizer: 第56回日本組織細胞化学会総会
  • Place of Presentation: 関西医科大学 （大阪府枚方市）
  • Year and Date: 2015-10-03
  • Invited
• [Presentation] 質量分析イメージングで何が見えるか (2015)
  • Author(s): 矢尾育子
  • Organizer: 第42回BMSコンファレンス
  • Place of Presentation: 岐阜グランドホテル （岐阜県岐阜市）
  • Year and Date: 2015-07-06
  • Invited
• [Presentation] Imaging mass spectrometry of acetylcholine for the nerve tissue sections. (2014)
  • Author(s): Yao I
  • Organizer: The 14th Kyungpook-Hamamatsu Joint Medical Symposium Hamamatsu Meeting
  • Place of Presentation: 浜松医科大学（静岡県浜松市）
  • Year and Date: 2014-09-25
• [Presentation] Mass spectrometry application for tissue imaging (2014)
  • Author(s): Ikuko Yao
  • Organizer: The Conference on Bioactive Peptides for Cell-Cell Communication 2014 - The 30th Anniversary of ANP (Atrial Natriuretic Peptide) Discovery
  • Place of Presentation: ホテルグランヴィア京都（京都府京都市）
  • Year and Date: 2014-09-12
  • Invited
• [Presentation] Synaptic localization of CaMKII in the spinal dorsal horn of kinase-dead knock-in mouse in the neuropathic pain model. (2014)
  • Author(s): 矢尾育子
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-11
• [Presentation] A type of cholinergic dysfunction involves cognitive deficit in a mouse model of Type 2 Diabetes Mellitus/Alzheimer’s disease. (2014)
  • Author(s): Matsuda T, Shibahara M, Yao I, Hisatsune T
  • Organizer: 第26回国際アルツハイマー病会議 （AAIC 2014)
  • Place of Presentation: コペンハーゲン（デンマーク）
  • Year and Date: 2014-07-13
• [Presentation] 脳内物質を対象とした質量分析イメージングの取り組みとその課題について (2014)
  • Author(s): 矢尾育子
  • Organizer: 第28回日本医用マススペクトル学会東海支部講演会
  • Place of Presentation: 名古屋大学（愛知県名古屋市）
  • Year and Date: 2014-06-28
  • Invited
• [Presentation] 臨床化学への応用に向けたイメージング質量分析の取り組み (2014)
  • Author(s): 矢尾育子
  • Organizer: 第 67 回日本臨床化学会近畿支部例会
  • Place of Presentation: 神戸薬科大学（兵庫県神戸市）
  • Year and Date: 2014-06-14
  • Invited
• [Presentation] 質量分析イメージングで可視化される生体分子情報 (2014)
  • Author(s): 矢尾育子
  • Organizer: バイオイメージ・インフォマティクスワークショップ（BIIWS）2014
  • Place of Presentation: 岡崎コンファレンスセンター（愛知県岡崎市）
  • Year and Date: 2014-06-09
• [Presentation] 脳情報の解読に向けた質量分析イメージングの取り組み (2014)
  • Author(s): 矢尾育子
  • Organizer: 第62回質量分析総合討論会
  • Place of Presentation: ホテル阪急エキスポパーク（大阪府吹田市）
  • Year and Date: 2014-05-15
  • Invited
• [Book] Lipid machinery investigation using MALDI imaging mass spectrometry. (2015)
  • Author(s): Yao I, Romero GA, Nicolaescu D, Setou M. (T Yokomizo ed)
  • Total Pages: 429
  • Publisher: "Bioactive Lipid Mediators: Current Reviews and Protocols" from Springer Japan
• [Book] 質量分析イメージングによる脳内環境の可視化(遺伝子医学MOOK 26号) (2014)
  • Author(s): 矢尾育子．（高橋良輔，漆谷真，山中宏二，樋口真人編)
  • Publisher: メディカルドゥ