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アラシキ ノブト
ARASHIKI Nobuto
新敷 信人 所属 医学部 医学科 職種 助教 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Cholesterol-binding protein TSPO2 coordinates maturation and proliferation of terminally differentiating erythroblasts. |
| 掲載誌名 | 正式名：The Journal of biological chemistry 略 称：J Biol Chem ISSNコード：1083351X/00219258 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 295(23),pp.8048-8063 |
| 著者・共著者 | Kiatpakdee Benjaporn, Sato Kota, Otsuka Yayoi, Arashiki Nobuto, Chen Yuqi, Tsumita Takuya, Otsu Wataru, Yamamoto Akito, Kawata Reo, Yamazaki Jumpei, Sugimoto Yoshikazu, Takada Kensuke, Mohandas Narla, Inaba Mutsumi |
| 発行年月 | 2020/05 |
| 概要 | TSPO2 (translocator protein 2) is a transmembrane protein specifically expressed in late erythroblasts and has been postulated to mediate intracellular redistribution of cholesterol. We identified TSPO2 as the causative gene for the HK (high K+) trait with immature red cell phenotypes in dogs and investigated the effects of the TSPO2 defects on erythropoiesis in HK dogs with the TSPO2 mutation and Tspo2 knockout (Tspo2-/- ) mouse models. Bone marrow-derived erythroblasts from HK dogs showed increased binucleated and apoptotic cells at various stages of maturation and shed large nuclei with incomplete condensation when cultured in the presence of erythropoietin, indicating impaired maturation and cytokinesis. The canine TSPO2 induces cholesterol accumulation in the endoplasmic reticulum and could thereby regulate cholesterol availability by changing intracellular cholesterol distribution in erythroblasts. Tspo2-/- mice consistently showed impaired cytokinesis with increased binucleated erythroblasts, resulting in compensated anemia and their red cell membranes had increased Na,K-ATPase, resembling the HK phenotype in dogs. Tspo2-deficient mouse ES cell-derived erythroid progenitor (MEDEP) cells exhibited similar morphological defects associated with a cell-cycle arrest at the G2/M phase, resulting in decreased cell proliferation and had a depletion in intracellular unesterified and esterified cholesterol. When the terminal maturation was induced, Tspo2-/- MEDEP cells showed delays in hemoglobinization, maturation-associated phenotypic changes in CD44, CD71, and TER119 expression, and cell-cycle progression. Taken together, these findings imply that TSPO2 is essential for coordination of maturation and proliferation of erythroblasts during normal erythropoiesis. |
| DOI | 10.1074/jbc.RA119.011679 |
| PMID | 32358067 |