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

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

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

Kiatpakdee, Benjaporn; Sato, Kota; Otsuka, Yayoi et al.

Journal of Biological Chemistry (JBC), 2020, 295(23), 8048-8063

Permalink : https://hdl.handle.net/2115/79035

このアイテムのアクセス数:934件（2026-10-07 16:38 集計）

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https://doi.org/10.1074/jbc.RA119.011679			14

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アクセス権	open access
URI	https://hdl.handle.net/2115/79035
タイトル	Cholesterol-binding protein TSPO2 coordinates maturation and proliferation of terminally differentiating erythroblasts
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
著者名 Kiatpakdee, Benjaporn
著者名 Sato, Kota
著者名 Otsuka, Yayoi
著者名 Arashiki, Nobuto
著者名 Chen, Yuqi
著者名 Tsumita, Takuya
著者名 Otsu, Wataru
著者名 Yamamoto, Akito
著者名 Kawata, Reo
著者名 Yamazaki, Jumpei
著者名 Sugimoto, Yoshikazu
著者名 Takada, Kensuke
著者名 Mohandas, Narla
e-Rad_Researcher 00183179 著者名 Inaba, Mutsumi
言語	英語
キーワード	cholesterol
	cytokinesis
	cell cycle
	erythropoiesis
	erythrocyte
	Na plus
	K plus -ATPase
	erythroblast
	TSPO2
発行日	2020-06-05
出版者	American Society for Biochemistry and Molecular Biology (ASBMB)
収録物名	Journal of Biological Chemistry (JBC)
巻(号)	295(23)
ページ	8048-8063
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
PISSN	0021-9258
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1074/jbc.RA119.011679