The regulatory mechanism and the role of CDM family protein in atherosclerosis

• Project/Area Number: 26870420
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry; Pathological medical chemistry
• Research Institution: University of Miyazaki (2015); Kyushu University (2014)
• Principal Investigator: Sanematsu Fumiyuki 宮崎大学, 医学部, 助教 (80381094)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マクロファージ / 動脈硬化 / マクロピノサイトーシス / 細胞骨格 / 泡沫細胞

Outline of Final Research Achievements

Foam cell formation through macropinocytosis in atherosclerosis pathophysiology has been already established. However, detailed mechanism remains to be determined. This study aims to analyze the role of DOCK1/2/5 as Rac activator in foam cell formation. We discovered that the uptake of dextran-FITC was significantly reduced in bone marrow macrophage of DOCK1/2/5 triple knockout mice. Treatment of CPYPP as DOCK 1/2/5 inhibitor in wild type bone marrow macrophage showed the similar result. We found that DOCK1/2/5 function links macropinocytosis formation, suggesting that DOCK1/2/5 participate in foam cell formation. It leads to elucidate their pathogenesis and develop novel therapies.

Research Products

• [Journal Article] Intronic regulation of Aire expression by Jmjd6 for self-tolerance induction in the thymus. (2015)
  • Author(s): Yanagihara T, Sanematsu F, Sato T, Uruno T, Duan X, Tomino T, Harada Y, Watanabe M, Wang Y, Tanaka Y, Nakanishi Y, Suyama M, Yoshinori F.
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 8820-8820
  • DOI: 10.1038/ncomms9820
  • Peer Reviewed / Open Access
• [Journal Article] DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation. (2014)
  • Author(s): Ogawa K, Tanaka Y, Uruno T, Duan X, Harada Y, et al.
  • Journal Title: J. Exp. Med. Volume: (In press) Issue: 7 Pages: 1407-1419
  • DOI: 10.1084/jem.20131926
  • Peer Reviewed / Open Access
• [Journal Article] DOCK2 and DOCK5 act additively in neutrophils to regulate chemotaxis, superoxide production, and extracellular trap formation. (2014)
  • Author(s): Watanabe M, Terasawa M, Miyano K, Yanagihara T, Uruno T, Sanematsu F, Nishikimi A, Cote JF, Sumimoto H, Fukui Y.
  • Journal Title: J Immunol. Volume: 193 Issue: 11 Pages: 5660-5667
  • DOI: 10.4049/jimmunol.1400885
  • Peer Reviewed / Open Access
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/iden/
• [Remarks] http://www.bioreg.kyushu-u.ac.jp/iden/