Analysis of molecular mechanism of cell protective function of Derlin-3

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K18510
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Eura Yuka (江浦由佳) 国立研究開発法人国立循環器病研究センター, 研究所, 研究員 (30443477)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ERAD / ER stress / Derlin-3 / Herp

Outline of Final Research Achievements

ER-associated degradation (ERAD) contributes to the maintenance of cellular homeostasis by degrading and eliminating structurally abnormal proteins generated in the endoplasmic reticulum. In this study, we focused on Derlin-3 whose expression is induced by endoplasmic reticulum stress and analyzed the importance of its function. In the in vivo experiments using hypoxic conditions, we found that Derlin-3 deficient mice exhibited the survival vulnerability. Herp (a protein forming an ERAD complex with Derlin-3)-deficient mice also exhibited the vulnerability. We also found that these mice have functional abnormalities in their hearts. Our findings that Herp controls the level of IP3 receptor, an intracellular signal transduction protein in the heart, may partly explain the cardiac abnormalities of Derlin-3 and Herp deficient mice.

Free Research Field

cell biology