Redox-dependent regulation of an endoplasmic reticulum resident protein in neural function

2014 Fiscal Year Final Research Report

• Project/Area Number: 24500451
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: HISATSUNE Chihiro 独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (10321803)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 酸化還元

Outline of Final Research Achievements

In this study, we found that ERp44, a factor involved in disulfide bond formation in the endoplasmic reticulum (ER), regulates angiotensin II. In mice, genetic loss of ERp44 destabilizes angiotensin II and causes hypotension. We found that ERp44 forms a mixed disulfide bond with ERAP1, an aminopeptidase that cleaves angiotensin II. ERp44 controls release of ERAP1 in a redox-dependent manner to control blood pressure. Additionally, we found that systemic inflammation triggers ERAP1 retention in the ER to inhibit hypotension. These results suggest that ERp44 redox-dependently regulates the intra- or extra-cellular localization of ERAP1, which contributes the control of serum angiotensin II level and blood pressure.

Free Research Field

分子生物学