Cdc42 regulates cell polarization and contractile actomyosin rings during terminal differentiation of human erythroblasts

Cdc42 regulates cell polarization and contractile actomyosin rings during terminal differentiation of human erythroblasts
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Cdc42在人成红细胞终末分化过程中调节细胞极化和收缩肌动球蛋白环

DOI:
10.1038/s41598-020-68799-1
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发表时间:
2020
期刊:
影响因子:
4.6
通讯作者:
Takahashi Naoto
Takahashi Naoto
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ubukawa Kumi;Goto Tatsufumi;Asanuma Ken;Sasaki Yumi;Guo Yong-Mei;Kobayashi Isuzu;Sawada Kenichi;Wakui Hideki;Takahashi Naoto

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通过比较去核和细胞分裂,阐明了成红细胞终末分化的分子机制。虽然各种相似之处和差异之间的成红细胞去核和胞质分裂已被报道,控制去核的机制仍然不清楚。我们以前报道过动力蛋白和微管组织中心介导了人成红细胞核的极化。此外,在成红细胞去核过程中注意到F-肌动蛋白的积累。因此,在去核过程中,上游效应在信号转导途径调节动力蛋白或肌动蛋白,如细胞分裂控制蛋白42同源物(Cdc 42),可能是至关重要的。我们在此研究了Cdc 42抑制剂卡辛对集落形成单位-红系细胞(CFU-Es)和成熟成红细胞(第10天)中胞质分裂和去核的影响。卡辛以剂量依赖性方式阻断CFU-Es的增殖和去核。动力蛋白在未处理的CFU-Es细胞质中呈岛状分布,但在CASIN处理的细胞中,动力蛋白集中在细胞核附近,呈点状,并与γ-微管蛋白共定位。卡辛阻断CFU-Es和第10天细胞中F-肌动蛋白的积累。这些结果表明Cdc 42通过与成红细胞终末分化过程中的动力蛋白和肌动蛋白丝组织的关系在胞质分裂、核极化和核挤出中起重要作用。
The molecular mechanisms involved in the terminal differentiation of erythroblasts have been elucidated by comparing enucleation and cell division. Although various similarities and differences between erythroblast enucleation and cytokinesis have been reported, the mechanisms that control enucleation remain unclear. We previously reported that dynein and microtubule-organizing centers mediated the polarization of nuclei in human erythroblasts. Moreover, the accumulation of F-actin was noted during the enucleation of erythroblasts. Therefore, during enucleation, upstream effectors in the signal transduction pathway regulating dynein or actin, such as cell division control protein 42 homolog (Cdc42), may be crucial. We herein investigated the effects of the Cdc42 inhibitor, CASIN, on cytokinesis and enucleation in colony-forming units-erythroid (CFU-Es) and mature erythroblasts (day 10). CASIN blocked the proliferation of CFU-Es and their enucleation in a dose-dependent manner. Dynein adopted an island-like distribution in the cytoplasm of non-treated CFU-Es, but was concentrated near the nucleus as a dot and co-localized with γ-tubulin in CASIN-treated cells. CASIN blocked the accumulation of F-actin in CFU-Es and day 10 cells. These results demonstrated that Cdc42 plays an important role in cytokinesis, nuclear polarization and nuclear extrusion through a relationship with dynein and actin filament organization during the terminal differentiation of erythroblasts.
DOI: 10.1038/ncomms9128
发表时间: 2015-08-26
影响因子: 16.6
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发表时间: 2012-05-04
期刊: CELL STEM CELL
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Oda,A.:“促红细胞生成素在原代培养的人红系前体细胞中诱导 Jak2、STAT5A 和 STAT5B 的酪氨酸磷酸化。”
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