Regulation of erythroblast maturation by TSPO2 through cholesterol accumulation in the endoplasmic reticulum

• Project/Area Number: 15K14861
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: INABA Mutsumi 北海道大学, 獣医学研究科, 教授 (00183179)
• Co-Investigator(Renkei-kenkyūsha): YAMAZAKI Jumpei 北海道大学, (連合)大学院獣医学研究院, 助教 (20732902)
• Research Collaborator: SATO Kota 北海道大学, (連合)大学院獣医学研究科, 准教授 (50283974)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 赤血球 / 赤芽球 / 成熟 / 脱核 / コレステロール / TSPO2 / 分化・成熟

Outline of Final Research Achievements

We previously found that the HK dog red cell phenotype is caused by some mutations in the TSPO2 (translocator protein 2) gene. We here analyzed the role of TSPO2 in the terminal maturation of erythroid cells. We showed that deletion of TSPO2 or its cholesterol-binding motif in erythroid lineage cells (late erythoroblasts) resulted in retardation or decreases in cell growth, cell cycle, exclusion of large non-condensed nuclei upon enucleation, and hemoglobin synthesis, resembling HK dog red cell phenotype. These findings suggest that TSPO2 regulates terminal maturation of late erythroblasts through its function in cholesterol metabolism.

Research Products

• [Int'l Joint Research] New York Blood Center(米国)