The molecular mechanism of ER stress response and the pathophysiology of ER stress disorders

2017 Fiscal Year Final Research Report

• Project/Area Number: 24228002
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Applied biochemistry
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Kohno Kenji 奈良先端科学技術大学院大学, 研究推進機構, 特任教授 (50142005)
• Co-Investigator(Kenkyū-buntansha): 都留 秋雄 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (80273861)
• Co-Investigator(Renkei-kenkyūsha): KIOKE Masaaki 奈良先端科学技術大学院大学, 研究推進機構, 特任助教 (60263448) ; KIMATA Yukio 奈良先端科学技術大学院大学, バイオサイエンス研究科, 准教授 (60263448) ; SAITO Michiko 京都薬科大学, バイオサイエンス研究センター, 准教授 (40379558)
• Research Collaborator: OHFURUDONO Miku ; RON David
• Project Period (FY): 2012-05-31 – 2017-03-31
• Keywords: 細胞応答 / 情報伝達

Outline of Final Research Achievements

Under physiological condition, ER stress pathway (IRE1 branch) is constitutively activated in pancreatic islet β cells and intestinal goblet cells, which secrete insulin and mucin, respectively. To clarify the physiological role of highly activated IRE1 pathway, we constructed Ire1α or Ire1β KO mice, and examined their physiological and molecular biological differences between wild-type and Ire1 KO mice. Islet β cell-specific Ire1α-conditional KO mice showed the typical diabetic phenotype due to the disorder of oxidative proinsulin folding. Ire1β KO mice showed the retardation of nematoda expulsion due to the impairment of mature mucin production in intestinal goblet cells. These results clearly indicate that highly activation of IRE1 pathway plays an important role in normal insulin-secretion and/or the maintenance of homeostasis of intestine under physiological condition.

Free Research Field

応用生物科学