Mechanism of the maintenance of ER homeostasis by redox regulation

2017 Fiscal Year Final Research Report

• Project/Area Number: 24227009
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Cell biology
• Research Institution: Kyoto Sangyo University
• Principal Investigator: NAGATA Kazuhiro 京都産業大学, 総合生命科学部, 教授 (50127114)
• Co-Investigator(Renkei-kenkyūsha): USHIODA Ryo 京都産業大学, 総合生命科学部, 研究助教 (30553367)
• Research Collaborator: MORITO Daisuke 京都産業大学, 主任研究員 ; YAMAMOTO Yohei 大阪大学, 助教 ; ITO Shinya 京都産業大学, 研究員
• Project Period (FY): 2012-05-31 – 2017-03-31
• Keywords: 小胞体 / カルシウム恒常性 / レドックス恒常性 / プロテオステイシス

Outline of Final Research Achievements

Three major homeostasis in the ER, protein, calcium ion and redox, are closely regulating each other through a crosstalk. We found a novel ER-resident reductase ERdj5 and revealed that ERdj5 plays a pivotal role in facilitating the ER-associated degradation (ERAD) of misfolded proteins. We found that ERdj5 is also involved in the regulation of calcium ion pump SERCA2b though its reducing activity. ERdj5 reduces the disulfide bond in the ER lumen of SERCA2b and activates its ATPase activity. When Ca2+ concentration in the ER lumen is low, ERdj5 reduces and activates the SERCA2b, but when Ca2+ is high enough, ERdj5 makes a oligomer, which is no more active in activating the SERCA2b. Thus, ERdj5 regulates the SERCA2b activity by sensing the Ca2+ concentration in the ER lumen. We also revealed that the redox homeostasis in the ER is interfered by the protein homeostasis in the cytosol, which suggests the crosstalk between cytosolic protein homeostasis and ER redox homeostasis.

Free Research Field

細胞生物学