Altering microtubule stability affects microtubule clearance and nuclear extrusion during erythropoiesis |
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Authors: | Songbo Xie Bing Yan Jie Feng Yuhan Wu Na He Lei Sun Jun Zhou Dengwen Li Min Liu |
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Institution: | 1. Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan, Shandong, China;2. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China
Xie and Yan have contributed equally to this work.;3. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China |
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Abstract: | Mammalian erythrocytes are highly specialized cells that have adapted to lose their nuclei and cellular components during maturation to ensure oxygen delivery. Nuclear extrusion, the most critical event during erythropoiesis, represents an extreme case of asymmetric partitioning that requires a dramatic reorganization of the cytoskeleton. However, the precise role of the microtubule cytoskeleton in the enucleation process remains controversial. In this study, we show that microtubule reorganization is critical for microtubule clearance and nuclear extrusion during erythropoiesis. Using a rodent anemia model, we found that microtubules were present in erythroblasts and reticulocytes but were undetectable in erythrocytes. Further analysis demonstrated that microtubules became disordered in reticulocytes and revealed that microtubule stabilization was critical for tubulin degradation. Disruption of microtubule dynamics using the microtubule-stabilizing agent paclitaxel or the microtubule-destabilizing agent nocodazole did not affect the efficiency of erythroblast enucleation. However, paclitaxel treatment resulted in the retention of tubulin in mature erythrocytes, and nocodazole treatment led to a defect in pyrenocyte morphology. Taken together, our data reveals a critical role for microtubules in erythrocyte development. Our findings also implicate the disruption of microtubule dynamics in the pathogenesis of anemia-associated diseases, providing new insight into the pathogenesis of the microtubule-targeted agent-associated anemia frequently observed during cancer chemotherapy. |
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Keywords: | erythrocyte erythropoiesis microtubule microtubule-targeted agent nuclear extrusion |
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