聴・平衡覚器官のイメージング解析～１分子から個体レベルまで～

2014 Fiscal Year Annual Research Report

• Project Area: Mutli-dimensional fluorescence live imaging of cellular function and molecular activity
• Project/Area Number: 25113715
• Research Institution: Kobe University
• Principal Investigator: 齋藤 尚亮 神戸大学, バイオシグナル研究センター, 教授 (60178499)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: Cdc42 / 内耳 / 有毛細胞 / イメージング

Outline of Annual Research Achievements

内耳有毛細胞特異的Cdc42 KOマウスが、1)「正常聴覚獲得後に多彩な聴毛の形態異常による緩徐進行性の75dB程度の高度難聴を呈する」、2)「Cdc42は聴毛の形成過程よりむしろ維持期に機能する」、3)「Cdc42は聴毛膜に局在する」 、4)「その活性化は聴毛の上半（先端）部の方が下半（基）部よりも強い（FRET法により証明）」等の４つの事実を世界に先駆けて明らかにした。
聴毛の形態異常については、欠損・短縮・伸長・癒合など所見を電子顕微鏡（図中矢印）にて明らかにした。このような聴毛の形態変化を引き起こす原因として、正常では聴毛及び頂側結合複合体（apical junctional complexes）に局在・活性化して、アクチン代謝を巧妙に調節しているCdc42が機能しないため、N-WASPによるアクチン重合とcofilinによるアクチン脱重合の両者が障害され、アクチン代謝が非常に低い状態で保たれるようになるためであることを証明した。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] The Extracellular A-loop of Dual Oxidases Affects the Specificity of Reactive Oxygen Species Release. (2015)
  • Author(s): Ueyama T, Sakuma M, Ninoyu Y, Hamada T, Dupuy C, Geiszt M, Leto TL, Saito N.
  • Journal Title: J Biol. Chem Volume: 290 Pages: 6495-6506
  • DOI: 10.1074/jbc.M114.592717.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification and characterization of PKCγ, a kinase associated with SCA14, as an amyloidogenic protein. (2015)
  • Author(s): Takahashi H, Adachi N, Shirafuji T, Danno S, Ueyama T, Vendruscolo M, Shuvaev AN, Sugimoto T, Seki T, Hamada D, Irie K, Hirai H, Sakai N, *Saito N.
  • Journal Title: Hum Mol Genet. Volume: 24 Pages: 525-539
  • DOI: 10.1093/hmg/ddu472
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of Pak-interacting exchange factor-β phosphorylation at serines 340 and 583 by PKCγ in dopamine release. (2014)
  • Author(s): Shirafuji T, Ueyama T, Yoshino K, Takahashi H, Adachi N, Ago Y, Koda K, Nashida T, Hiramatsu N, Matsuda T, Toda T, Sakai N, Saito N.
  • Journal Title: J Neurosci. Volume: 34 Pages: 9268-9280
  • DOI: 10.1523/JNEUROSCI.4278-13.2014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Maintenance of stereocilia and apical junctional complexes by Cdc42 in cochlear hair cells. (2014)
  • Author(s): Ueyama T, Sakaguchi H, Nakamura T, Goto A, Morioka S, Shimizu A, Nakao K, Hishikawa Y, Ninoyu Y, Kassai H, Suetsugu S, Koji T, Fritzsch B, Yonemura S, Hisa Y, Matsuda M, Aiba A, Saito N.
  • Journal Title: J Cell Sci. Volume: 127 Pages: 2040-2052
  • DOI: 10.1242/jcs.143602.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Heparin inhibits melanosome uptake and inflammatory response coupled with phagocytosis through blocking PI3k/Akt and MEK/ERK signaling pathways in human epidermal keratinocytes. (2014)
  • Author(s): Makino-Okamura C, Niki Y, Takeuchi S, Nishigori C, Declercq L, Yaroch DB, Saito N.
  • Journal Title: Pigment Cell Melanoma Res. Volume: 27 Pages: 1063-1074
  • DOI: 10.1111/pcmr.12287.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCa signaling pathway (2014)
  • Author(s): Maillard, L., Saito, N., Hlawaty, H., Friand, V., Suffee, N., Chmilewsky, F., Haddad, O., Laguillier, C., Guyot, E., Ueyama, T., Oudar, O., Sutton, A., Charnaux, N.
  • Journal Title: Biology Open Volume: 3 Pages: 995-1004
  • DOI: 10.1242/bio.20148227
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Both the C1 domain and a basic amino acid cluster at C-terminus are important for neurite and branch induction ability of DGKb (2014)
  • Author(s): Takuya Kano, Takeshi Kouzuki, Satoru Mizuno, Shuji Ueda, Minoru Yamanoue, Fumio Sakane, Naoaki Saito and Yasuhito Shirai
  • Journal Title: Biochem. Biophys. Res. Commun, Volume: 447 Pages: 89-94
  • DOI: 10.1016/j.bbrc.2014.03.113.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Diacylglycerol kinase gamma regulates antigen-induced mast cell degranulation by mediating Ca2+ influxes (2014)
  • Author(s): Sakuma, M., Shirai, Y., Ueyama, T., and Saito, N.
  • Journal Title: Biochem. Biophys. Res. Commun, Volume: 445 Pages: 340-345
  • DOI: 10.1016/j.bbrc.2014.01.197
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 内耳有毛細胞におけるRhoファミリー低分子量G蛋白質の役割 (2014)
  • Author(s): 上山健彦、齋藤尚亮
  • Organizer: 日本組織細胞化学会
  • Place of Presentation: 松本
  • Year and Date: 2014-09-27 – 2014-09-28
• [Presentation] Cdc42 is required for maintenance of stereocilia and apical junctional complexes in cochlear hair cells. (2014)
  • Author(s): Ueyama, T., Sakaguchi, H., Goto, A., Hisa, Y., Matsuda, M., Aiba, A. and Saito, N.
  • Organizer: The 37th Naito Conference
  • Place of Presentation: 北海道ニセコ
  • Year and Date: 2014-07-15 – 2014-07-18