Mechanism of misfolded protein transportation to outside cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670143
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Osaka University
• Principal Investigator: ARASE Hisashi 大阪大学, 微生物病研究所, 教授 (10261900)
• Co-Investigator(Renkei-kenkyūsha): KOHYAMA Masako 大阪大学, 微生物病研究所, 助教 (70311339) ; SUENAGA Tadahiro 大阪大学, 微生物病研究所, 助教 (20396675) ; HIRAYASU Kouyuki 大阪大学, 免疫学フロンティア研究センター, 特任助教 (30585170)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ミスフォールドタンパク質 / 分子シャペロン / MHCクラスⅡ / 自己抗体 / 自己免疫疾患

Outline of Final Research Achievements

We have identified MHC class II molecules as a molecule that transports cellular misfolded MHC class I molecules to the cell surface. When we analyzed other proteins, hen egg lysozeme, immunoglobulin heavy chain and β2-glycoprotein I were also transported to the cell surface by MHC class II molecules upon association with MHC class II molecules. Furthermore, these misfolded proteins transported to the cell surface by MHC class II molecules were found to be specific targets for autoantibodies produced in rheumatoid arthritis and antiphospholipid syndrome. In order to identify molecules that transport misfolded proteins to the cell surface, we analyzed molecules that associate with misfolded proteins at the cell surface. We found that several molecules are associated with misfolded proteins by mass spectrometry.

Free Research Field

医歯薬学