Abstract:
:Mammalian erythroblasts undergo enucleation through a process thought to be similar to cytokinesis. Microtubule-organizing centers (MTOCs) mediate organization of the mitotic spindle apparatus that separates the chromosomes during mitosis and are known to be crucial for proper cytokinesis. However, the role of MTOCs in erythroblast enucleation remains unknown. We therefore investigated the effect of various MTOC inhibitors on cytokinesis and enucleation using human colony-forming units-erythroid (CFU-Es) and mature erythroblasts generated from purified CD34(+) cells. We found that erythro-9-[3-(2-hydroxynonyl)]adenine (EHNA), a dynein inhibitor, and monastrol, a kinesin Eg5 inhibitor, as well as various inhibitors of MTOC regulators, including ON-01910 (Plk-1), MLN8237 (aurora A), hesperadin (aurora B), and LY294002 (PI3K), all inhibited CFU-E cytokinesis. Among these inhibitors, however, only EHNA blocked enucleation. Moreover, terminally differentiated erythroblasts expressed only dynein; little or none of the other tested proteins was detected. Over the course of the terminal differentiation of human erythroblasts, the fraction of cells with nuclei at the cell center declined, whereas the fraction of polarized cells, with nuclei shifted to a position near the plasma membrane, increased. Dynein inhibition impaired nuclear polarization, thereby blocking enucleation. These data indicate that dynein plays an essential role not only in cytokinesis but also in enucleation. We therefore conclude that human erythroblast enucleation is a process largely independent of MTOCs, but dependent on dynein.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Kobayashi I,Ubukawa K,Sugawara K,Asanuma K,Guo YM,Yamashita J,Takahashi N,Sawada K,Nunomura Wdoi
10.1016/j.exphem.2015.12.003subject
Has Abstractpub_date
2016-04-01 00:00:00pages
247-56.e12issue
4eissn
0301-472Xissn
1873-2399pii
S0301-472X(15)00800-0journal_volume
44pub_type
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journal_title:Experimental hematology
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pub_type: 杂志文章
doi:
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更新日期:2014-09-01 00:00:00
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journal_title:Experimental hematology
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更新日期:1976-09-01 00:00:00
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更新日期:2015-10-01 00:00:00
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doi:
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journal_title:Experimental hematology
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doi:
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journal_title:Experimental hematology
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doi:
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journal_title:Experimental hematology
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doi:
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