Roles of heparan sulfate modification in biological signaling

• Project/Area Number: 25293065
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: University of Tsukuba
• Principal Investigator: Masu Masayuki 筑波大学, 医学医療系, 教授 (20243032)
• Co-Investigator(Kenkyū-buntansha): KEINO-MASU Kazuko 筑波大学, 医学医療系, 講師 (50344883)
• Co-Investigator(Renkei-kenkyūsha): NAGATA Michio 筑波大学, 医学医療系, 教授 (10192238)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: ヘパラン硫酸 / 糖鎖 / スルファターゼ / ノックアウトマウス / 脳 / 腎臓 / 糖尿病 / 遺伝子 / シグナル伝達

Outline of Final Research Achievements

We performed analysis of heparan sulfate endosulfatases, Sulf1 and Sulf2, in biological signaling by using knockout mice. The double knockout mice showed corticospinal tract defects, including defects in midline crossing at the pyramidal decussation and abnormal trajectory towards the superior colliculus. The double knockout mice also showed slight abnormalities in kidney glomeruli, especially in the mesangial region. Furthermore they showed severer glomerular abnormalities after inducing diabetes mellitus by streptozotocin compared with the wild-type controls.

Research Products

• [Int'l Joint Research] Radbout University(オランダ)
• [Journal Article] Heparan Sulfate 6-O-EndoSulfatases, Sulf1 and Sulf2, Regulate Glomerular Integrity by Modulating Growth Factor Signaling. (2016)
  • Author(s): Takashima, Y., Keino-Masu, K., Yashiro, H., Hara, S., Suzuki, T., van Kuppevelt, T.H., Masu, M., and Nagata, M.
  • Journal Title: American Journal of Physiology Renal Physiology Volume: 310
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Proteoglycans and axon guidance: a new relationship between old partners. (2016)
  • Author(s): Masu, M.
  • Journal Title: Journal of Neurochemistry Volume: in press Issue: S2 Pages: 58-75
  • DOI: 10.1111/jnc.13508
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expression of the heparan sulfate 6-0-endosulfatases, Sulfl and Sulf2, in the avian and mammalian inner earsuggests a role for sulfation during inner ear development. (2014)
  • Author(s): Freeman SD, Keino-Masu K, Masu M, Ladher RK.
  • Journal Title: Developmental Dynamics Volume: 244 Issue: 2 Pages: 168-180
  • DOI: 10.1002/dvdy.24223
  • Peer Reviewed / Open Access
• [Journal Article] ErbB2 dephosphorylation and anti-proliferative effects of neuregulin-1 in ErbB2-overexpressing cell lines; re-evaluation of their low-affinity interaction. (2013)
  • Author(s): Wang, R., Iwakura, Y., Araki, K., Keino-Masu, K., Masu, M., Wang, X., Takei, N., Higashiyama, S. and Nawa, H.
  • Journal Title: Scientific reports Volume: 3 Issue: 1 Pages: 1402-1402
  • DOI: 10.1038/srep01402
  • Peer Reviewed
• [Journal Article] A unique mouse model for investigating the properties of amyotrophic lateral sclerosis-associated protein TDP-43, by in utero electroporation. (2013)
  • Author(s): Akamatsu, M., Takuma, H., Yamashita, T., Okada, T., Keino-Masu, K., Ishii, K., Kwak, S., Masu, M., and Tamaoka, A.
  • Journal Title: Neuroscience Research Volume: 77 Issue: 4 Pages: 234-241
  • DOI: 10.1016/j.neures.2013.09.009
  • NAID: 120007130577
  • Peer Reviewed
• [Journal Article] ヘパラン硫酸微細構造の組織特異性とその決定機構 (2013)
  • Author(s): 桝和子、桝正幸.
  • Journal Title: 医学のあゆみ Volume: 245 Pages: 600-602
  • Peer Reviewed
• [Presentation] Wntシグナル伝達因子CCD1のDIXドメインを介する新規な自己活性抑制制御の構造基盤の解明 (2015)
  • Author(s): 藤田祥平、寺脇慎一、塩見健輔、桝和子、桝正幸、若松馨、柴田直樹、樋口芳樹
  • Organizer: 日本分子生物学年会・日本生化学会大会合同大会
  • Place of Presentation: 神戸国際会議場（兵庫県）
  • Year and Date: 2015-12-01
• [Presentation] 糸球体Sulf1/2は腎機能維持に不可欠である (2015)
  • Author(s): 高島康利、屋代紘、桝和子、桝正幸、長田道夫
  • Organizer: 日本糖質学会年会
  • Place of Presentation: 東京大学安田講堂（東京都）
  • Year and Date: 2015-07-30
• [Presentation] A role of neurotrophin signaling in the migration and nucleogenesis of precerebellar neurons. (2015)
  • Author(s): Takuya Okada, Kazuko Keino-Masu, Masayuki Masu
  • Organizer: 日本神経科学学会大会
  • Place of Presentation: 神戸国際会議場（兵庫県）
  • Year and Date: 2015-07-28
• [Presentation] ゼブラフィッシュCCD1 DIXドメインのX線結晶解析X-ray crystallographic analysis of zebrafish CCD1 DIX domai (2015)
  • Author(s): 藤田祥平、寺脇慎一、塩見健輔、桝和子、桝正幸、若松馨、柴田直樹、樋口芳樹
  • Organizer: 第32回PFシンポジウム
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2015-03-17 – 2015-03-18
• [Presentation] Analysis of the corticospinal tract formation in adult Sulf1;Sulf2 double knockout mice (2014)
  • Author(s): Takuya Okada, Nana Kagaya, Kazuko Keino-Masu, Masayuki Masu
  • Organizer: 第37回日本神経科学学会大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Electron microscopic observation of intranuclear aggregation of TDP-43 in mouse cerebral cortex produced by in utero electroporation (2014)
  • Author(s): Megumi Akamatsu, Hiroshi Takuma, Takenari Yamashita, Takuya Okada, Kazuko Keino-Masu, Hartmut Oehring, Shin Kwak, Masayuki Masu, Gustav F Jirikowski, Akira Tamaoka
  • Organizer: 第37回日本神経科学学会大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] 子宮内電気穿孔法TDP-43 遺伝子導入によるin vivo形成封入体の微細形態の検討 (2014)
  • Author(s): 詫間浩、赤松恵、山下雄也、Oehring, H.、岡田拓也、桝和子、石井一弘、Jirikowski, G、郭伸、桝正幸、玉岡晃
  • Organizer: 第55回日本神経学会総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] Heparan sulfate modification by endosulfatases Sulf1 and Sulf2 is required for the cotricospinal tract formation (2014)
  • Author(s): Kazuko Keino-Masu, Takuya Okada, Masayuki Masu.
  • Organizer: International Symposium on Glyco-Neuroscience
  • Place of Presentation: Awaji Yumebutai International Conference Center（Hyogo）
• [Presentation] ヘパラン硫酸エンドスルファターゼSulf1の嗅覚記憶における役割 (2013)
  • Author(s): 桝和子、奥谷文乃、椛秀人、桝正幸
  • Organizer: 第36回日本神経科学学会大会・第56回日本神経化学会大会・第30回日本神経回路学会大会
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] マウス胎仔電気穿孔法による in vivo TDP-43 遺伝子導入と封入体形成の検討 (2013)
  • Author(s): 詫間浩、赤松恵、山下雄也、岡田拓也、石井一弘、桝和子、郭伸、桝正幸、玉岡晃
  • Organizer: 第54回日本神経学会総会
  • Place of Presentation: 東京国際フォーラム（東京）
• [Presentation] 筋萎縮性側索硬化症関連タンパク：TDP-43封入体の形成-マウス胎児電気穿孔法による大脳皮質運動野への疾患関連遺伝子の導入 (2013)
  • Author(s): 赤松恵、詫間浩、山下雄也、岡田拓也、石井一弘、桝和子、郭伸、桝正幸、玉岡晃
  • Organizer: 第36回日本神経科学学会大会・第56回日本神経化学会大会・第30回日本神経回路学会大会
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] Ccd1/Dixdc1欠損マウスにおける行動異常 (2013)
  • Author(s): 桝正幸、昌子浩孝、塩見健輔、宮川剛、桝和子
  • Organizer: 第36回日本神経科学学会大会・第56回日本神経化学会大会・第30回日本神経回路学会大会
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] Extracellular sulfatases regulate PDGF signaling and promotes nephropathy in diabetes. (2013)
  • Author(s): Takashima, Y., Yashiro, H., Masu, M. Keino-Masu, K., and Nagata, M .
  • Organizer: Kidney week 2012
  • Place of Presentation: Atlanta, USA
• [Presentation] TDP-43 aggregation produced by In utero electroporation and its properties in the mouse motor neurons
  • Author(s): Akamatsu, M., Takuma, H., Yamashita, T., Okada, T., Ishii, K., Keino-Masu, K., Kwak, S., Masu, M., Tamaoka, A.
  • Organizer: 43th Annual Meeting of Society for Neuroscience
  • Place of Presentation: San Diego Convention Center, San Diego, USA
• [Book] Cortical Development: Neural Diversity and Neocortical Organization (2013)
  • Author(s): Masu, M.
  • Total Pages: 320
  • Publisher: Springer-Verlag
• [Book] Lysophospholipid Receptors: Signaling and Biochemistry. (2013)
  • Author(s): Masu, M., Koike, S., Okada, T., and Keino-Masu, K.
  • Total Pages: 812
  • Publisher: John Wiley & Son Inc
• [Remarks] 筑波大学 医学医療系 分子神経生物学グループ
  • URL: http://www.md.tsukuba.ac.jp/basic-med/molneurobiol/
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/duo/molneurobiol/