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Cholesterol-binding protein TSPO2 coordinates maturation and proliferation of terminally differentiating erythroblasts

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Title: Cholesterol-binding protein TSPO2 coordinates maturation and proliferation of terminally differentiating erythroblasts
Authors: Kiatpakdee, Benjaporn Browse this author
Sato, Kota Browse this author
Otsuka, Yayoi Browse this author
Arashiki, Nobuto Browse this author
Chen, Yuqi Browse this author
Tsumita, Takuya Browse this author
Otsu, Wataru Browse this author
Yamamoto, Akito Browse this author
Kawata, Reo Browse this author
Yamazaki, Jumpei Browse this author
Sugimoto, Yoshikazu Browse this author
Takada, Kensuke Browse this author
Mohandas, Narla Browse this author
Inaba, Mutsumi Browse this author →KAKEN DB
Keywords: cholesterol
cell cycle
Na plus
K plus -ATPase
Issue Date: 5-Jun-2020
Publisher: American Society for Biochemistry and Molecular Biology (ASBMB)
Journal Title: Journal of Biological Chemistry (JBC)
Volume: 295
Issue: 23
Start Page: 8048
End Page: 8063
Publisher DOI: 10.1074/jbc.RA119.011679
Abstract: 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 embryonic stem cell?derived erythroid progenitor (MEDEP) cells exhibited similar morphological defects associated with a cell-cycle arrest at the G(2)/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.
Type: article
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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