Structure and function of the zipper-like structure

• Project/Area Number: 25462873
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Showa University
• Principal Investigator: Takito Jiro 昭和大学, 歯学部, 助教 (00197237)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Masanori 昭和大学, 歯学部, 教授 (50180394)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 破骨細胞 / 細胞骨格 / 細胞内小器官 / 細胞融合 / 細胞接着 / アクチン / ポドゾーム / 情報交換

Outline of Final Research Achievements

Osteoclasts are multinucleated giant cells that resorb bone. We previously reported that the podosome belt transforms into another superstructure, called the zipper-like structure (ZLS), at the cell contact site of two osteoclasts. To assess the role the ZLS in osteoclast fusion, we examined the static and dynamic dynamic structure of the ZLS in the osteoclast-like cells differentiated from RAW 264.7 cells. Immunofluorescence showed that the transformation of the podosome belt into the ZLS was associated with a rearrangement of component proteins. Live-cell imaging using EGFP-actin showed that the ZLS exhibited consistent symmetrical retrograde actin flow. We next examined signaling network that forms or maintains the ZLS. M-CSF, Rac1, Src and dynamin were positive regulators of the ZLS formation, whereas RhoA was a negative regulator. These molecules also affect osteoclast multinucleation. Thus, we concluded that the ZLS was positively involved in osteoclast fusion.

Research Products

• [Journal Article] Regulation of Osteoclast Multinucleation by the Actin Cytoskeleton Signaling Network. (2014)
  • Author(s): Takito J, Otsuka H, Yanagisawa N, Arai H, Shiga M, Inoue M, Nonaka N, Nakamura M
  • Journal Title: J Cell Physiol Volume: 230 Issue: 2 Pages: 395-405
  • DOI: 10.1002/jcp.24723
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 破骨細胞に見られるアクチン超構造体の静的構造 (2016)
  • Author(s): 瀧戸二郎、中村雅典
  • Organizer: 第１２１回日本解剖学会総会
  • Place of Presentation: 福島県郡山
  • Year and Date: 2016-03-28
• [Presentation] The anatomy of the zipper-like structure in osteoclast-like cells (2015)
  • Author(s): Jiro Takito & Masanori Nakamura
  • Organizer: Japanese Association for Dental Research
  • Place of Presentation: 福岡
  • Year and Date: 2015-10-30
  • Int'l Joint Research
• [Presentation] エンドサイトーシスと細胞融合に関与するアクチン再構築系の分離 (2015)
  • Author(s): 瀧戸 二郎
  • Organizer: 日本解剖学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] アクチン細胞骨格を制御するシグナルネットワークによる破骨細胞多核化の調節 (2014)
  • Author(s): 瀧戸二郎、中村雅典
  • Organizer: 第１１９回日本解剖学会総会
  • Place of Presentation: 栃木 自治医科大学
• [Presentation] Regulation of osteoclast multinucleation by the signaling network of actin cytoskeleton (2013)
  • Author(s): Jiro Takito, Hirotada Otsuka, Nobuaki Yanagisawa, Hiroshi Arai, Masayasu Shiga, Mitsuko Inoue, Naoko Nonaka, Masanori Nakamura
  • Organizer: Annual Meeting of The American Society for Cell Biology
  • Place of Presentation: New Orleans, Louisiana, USA