dual-function stress response protein

• Project/Area Number: 25462921
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Nagasaki University
• Principal Investigator: HOTOKEZAKA Yuka 長崎大学, 病院(歯学系), 講師 (10244089)
• Co-Investigator(Kenkyū-buntansha): KATAYAMA Ikuo 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (80295089) ; TASHIRO Shigeki 長崎大学, 病院(医学系), 助教 (20300882) ; EIDA Sato 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (80325662) ; NAKAMURA Takashi 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30172406)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: γ-taxilin / αNAC / ER stress / Alzheimer’s diseases / hypoxia / アルツハイマー病 / DNA障害修復 / alpha NAC / cleaved alpha NAC / MUC1

Outline of Final Research Achievements

The signaling pathway leading to the endoplasmic reticulum (ER) stress responses has not been fully elucidated. Here we showed that glycogen synthase kinase-3β (GSK-3β)-dependent downregulation of γ-taxilin and nascent polypeptide-associated complex α-subunit (αNAC) mediates hypoxia-induced unfolded protein responses (UPRs) and the subsequent apoptotic pathways. However, the ER stress signaling pathways initiated by γ-taxilin or αNAC were distinct, triggering different ER stress sensors and activating different downstream pathways. γ-taxilin ablation induced tau hyperphosphorylation alone. Notably, downregulation of γ-taxilin and αNAC occurs in the brain of patients with Alzheimer’s disease. These results suggest that γ-taxilin and αNAC merge to regulate hypoxia-induced ER stress responses and provide a new insight into the pathogenesis of Alzheimer’s diseases.

Research Products

• [Int'l Joint Research] Massachusetts General Hospital(米国)
• [Journal Article] Length of intact plasma membrane determines the diffusion properties of cellular water (2016)
  • Author(s): Sato Eida, Marc Van Cauteren, Yuka Hotokezaka, Ikuo Katayama, Miho Sasaki, Makoto Obara, Tomoyuki Okuaki, Misa Sumi, Takashi Nakamura
  • Journal Title: Scientific Reports Volume: 6 ;19051 Issue: 1 Pages: 1-10
  • DOI: 10.1038/srep19051
  • NAID: 120006987227
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] GSK-3β-dependent downregulation of γ-taxilin and αNAC merge to regulate ER stress responses. (2015)
  • Author(s): Hotokezaka Y, Katayama I, van Leyen K, Nakamura T
  • Journal Title: Cell Death and Disese Volume: 6
  • NAID: 120006987615
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] GSK-3β-dependent downregulation of γ-taxilin and αNAC merge to regulate ER stress responses. (2015)
  • Author(s): Hotokezaka Y, Katayama I, van Leyen K, Nakamura T.
  • Journal Title: Cell Death Dis Volume: 6 Issue: 4 Pages: e1719-e1719
  • DOI: 10.1038/cddis.2015.90
  • NAID: 120006987615
  • Peer Reviewed / Open Access / Acknowledgement Compliant