Identification and characterization of WDR6, a novel insulin signaling molecule

• Project/Area Number: 20790306
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Nagasaki University
• Principal Investigator: CHIBA Takuya Nagasaki University, 大学院・医歯薬学総合研究科, 准教授 (40336152)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 老化 / インスリンシグナル / カロリー制限 / 視床下部 / 代謝 / 寿命 / 神経内分泌 / インスリン

Research Abstract

We have isolated WD-repeat protein 6 (WDR6), a novel hypothalamus enriched gene in rat brain tissue. Amino acid sequence revealed that WDR6 have protein phosphatase motif and WD-repeat motif that have important roles for dephosphorylation and protein-protein interaction, respectively. Our study revealed that WDR6 physically interacted with insulin receptor substare-4 (IRS-4), which is abundantly expressed in the hypothalamus. These results suggest that WDR6 could regulate insulin/IGF-I signal in brain. Further study on WDR6 functions might contribute to the development of drugs for the treatment of neurodegenerative diseases, such as cognitive disorders.

Research Products

• [Journal Article] Identification and characterization of an insulin receptor substrate 4-interacting protein in rat brain: implications for longevity. (2009)
  • Author(s): Chiba T, Inoue D, Mizuno A, Komatsu T, Fujita S, Kubota H, Guimaraes M, Park S, Trindade L, Hayashida T, Hayashi H, Yamaza H, Higami Y, Shimokawa I
  • Journal Title: Neurobiol Aging 30(3) Pages: 474-82
  • Peer Reviewed
• [Journal Article] Divergent regulation of adipose tissue metabolism by calorie restriction and inhibition of growth hormone signaling. (2009)
  • Author(s): Park S, Komatsu T, Hayashi H, Trindade L, Yamaza H, Chiba T, Shimokawa I
  • Journal Title: Exp Gerontol 44(10) Pages: 646-52
  • NAID: 120006983879
  • Peer Reviewed
• [Journal Article] Similar metabolic responses to calorie restriction in lean and obese Zucker rats. (2009)
  • Author(s): Chiba T, Komatsu T, Nakayama M, Adachi T, Tamashiro Y, Hayashi H, Yamaza H, Higami Y, Shimokawa I
  • Journal Title: Mol Cell Endocrinol 309(1-2) Pages: 17-25
  • Peer Reviewed
• [Journal Article] Neuropeptide Yによる代謝制御と抗老化作用-ヒトへの応用に向けたCR mimetics開発の標的探索- (2009)
  • Author(s): 千葉卓哉, 下川功
  • Journal Title: 基礎老化研究 33(3) Pages: 17-20
  • Peer Reviewed
• [Journal Article] カロリー制限による抗老化作用:代謝適応仮説とヒトへの応用の可能性 (2009)
  • Author(s): 千葉卓哉, 下川功
  • Journal Title: アンチエイジング医学 5(4) Pages: 53-61
  • NAID: 40016808385
• [Journal Article] Similar metabolic responses to calorie restriction in lean and obese Zucker rats. (2009)
  • Author(s): Chiba T
  • Journal Title: Mol Cell Endocrinol 309(1-2) Pages: 17-25
  • Peer Reviewed
• [Journal Article] Identification and characterization of an insulin receptor substrate 4-interacting protein in rat brain : implications for longevity. (2009)
  • Author(s): Chiba T
  • Journal Title: Neurobiol Aging 30(3) Pages: 474-482
  • Peer Reviewed
• [Journal Article] Identification and characterization of an insulin receptor substrate 4-interacting protein in rat brain : implications for longevity (2009)
  • Author(s): Chiba T, et.al.
  • Journal Title: Neurobiol Aging 30(3) Pages: 474-482
  • Peer Reviewed
• [Journal Article] Pituitary growth hormone suppression reduces resistin expression and enhances insulin effectiveness: relationship with caloric restriction. (2008)
  • Author(s): Chiba T, Yamaza H, Komatsu T, Nakayama M, Fujita S, Hayashi H, Higami Y, Shimokawa I.
  • Journal Title: Exp Gerontol 43(6) Pages: 595-600
  • Peer Reviewed
• [Journal Article] Manipulation of caloric content but not diet composition, attenuates the deficit in learning and memory of senescence-accelerated mouse strain P8. (2008)
  • Author(s): Komatsu T, Chiba T, Yamaza H, Yamashita K, Shimada A, Hoshiyama Y, Henmi T, Ohtani H, Higami Y, de Cabo R, Ingram DK, Shimokawa I
  • Journal Title: Exp Gerontol 43(4) Pages: 339-46
  • Peer Reviewed
• [Journal Article] Akt/PKCζ/λ-Glut4 pathway in rat white adipose tissue in an insulin-independent manner. (2008)
  • Author(s): Park S, Komatsu T, Hayashi H, Yamaza H, Chiba T
  • Journal Title: AGE 30 Pages: 293-302
  • Peer Reviewed
• [Journal Article] Longevity Genes: Insights from Calorie Restriction and Genetic Longevity Models. (2008)
  • Author(s): Shimokawa I, Chiba T, Yamaza H, Komatsu T
  • Journal Title: Mol Cells 26(5) Pages: 427-435
• [Journal Article] Calorie restriction minimizes activation of insulin signaling in response to glucose: potential involvement of the growth hormone-insulin-like growth factor 1 axis. (2008)
  • Author(s): Hayashi H, Yamaza H, Komatsu T, Park S, Chiba T, Higami Y, Nagayasu T, Shimokawa I
  • Journal Title: Exp Gerontol 43(9) Pages: 827-32
  • NAID: 120006981679
  • Peer Reviewed
• [Journal Article] カロリー制限による寿命延長・抗老化機構-神経内分泌仮説に基づく代謝調節の重要性 (2008)
  • Author(s): 千葉卓哉, 山座治義, 下川功
  • Journal Title: 基礎老化研究 32(3 Pages: 15-20
  • NAID: 10024377776
  • Peer Reviewed
• [Presentation] Beneficial effects of calorie restriction: involvement of neuroendocrine system (2009)
  • Author(s): Chiba T
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] Beneficial effects of calorie restriction : involvement of neuroendocrine system. (2009)
  • Author(s): Chiba T
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] カロリー制限による抗老化作用の分子メカニズム:代謝・老化・寿命調節における中枢の役割 (2009)
  • Author(s): 千葉卓哉
  • Organizer: 第32回日本基礎老化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2009-06-20
• [Presentation] カロリー制限による代謝の変化におけるneuropeptide Yの重要性 (2009)
  • Author(s): 千葉卓哉
  • Organizer: 第32回日本基礎老化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2009-06-20
• [Presentation] Anti-aging effects of calorie restriction: Importance of neuroendocrine adaptation (2009)
  • Author(s): Chiba T
  • Organizer: The 2nd Hallym-Nagasaki international joint meeting on aging and neurodegenerative diseases
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2009-03-09
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/pathlgy1/index/index.htm
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/pathlgy1/index/index.htm
• [Patent(Industrial Property Rights)] カロリー制限模倣物のスクリーニング方法 (2009)
  • Inventor(s): 千葉卓哉 土谷 智史、下川 功、国立大学法人長崎大学
  • Industrial Property Rights Holder: 千葉卓哉 土谷 智史、下川 功、国立大学法人長崎大学
  • Industrial Property Number: 2009-189136
  • Filing Date: 2009-08-18
• [Patent(Industrial Property Rights)] カロリー制限模倣物のスクリーニング方法 (2009)
  • Inventor(s): 千葉卓哉、土谷智史、下川功、国立大学法人長崎大学
  • Industrial Property Rights Holder: 千葉卓哉、土谷智史、下川功、国立大学法人長崎大学
  • Industrial Property Number: 2009-189136
  • Filing Date: 2009-08-18
• [Patent(Industrial Property Rights)] Gene related to life extension and use thereof (2008)
  • Inventor(s): 千葉卓哉 下川 功、樋上 賀一、山座 治義、国立大学法人長崎大学
  • Industrial Property Rights Holder: 千葉卓哉 下川 功、樋上 賀一、山座 治義、国立大学法人長崎大学
  • Filing Date: 2008-09-18