Profilin 1 is required for abscission during late cytokinesis of chondrocytes
Profilin 1 is required for abscission during late cytokinesis of chondrocytes
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DOI：
10.1038/emboj.2009.58
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发表时间：
2009-04-22
期刊：
影响因子：
11.4
通讯作者：
Faessler, Reinhard
中科院分区：
文献类型：
--
作者：
Boettcher, Ralph T.;Wiesner, Sebastian;Faessler, Reinhard
Profilins是肌动蛋白细胞骨架动态重排的关键因素。然而，profilins在分化的哺乳动物细胞中的功能是不确定的，因为profilin缺陷是早期胚胎致死的高等真核生物。为了检查软骨细胞中的profilin功能，我们破坏了软骨中的profilin 1基因（Col 2 pfn 1）。纯合子Col 2 pfn 1小鼠发生由生长板解体和软骨细胞胞质分裂缺陷引起的进行性软骨发育不良，表现为双核细胞的出现。令人惊讶的是，Col 2 pfn 1软骨细胞在细胞分裂期间正常组装和收缩肌动球蛋白环;然而，它们在后期胞质分裂期间显示缺陷，因为它们由于不能产生强大的牵引力而经常无法完成分裂。这种力产生的减少是由于片状伪足、局灶性粘连和应力纤维的形成受损造成的，这在一定程度上可能与mDia 1介导的肌动蛋白丝伸长受损有关。无论是肌动蛋白还是聚脯氨酸结合缺陷型profilin 1都不能挽救缺陷。两者合计，我们的研究结果表明，profilin 1是不需要的肌动球蛋白环的形成在分裂的软骨细胞，但有必要产生足够的力，在后期胞质分裂的分裂。
Profilins are key factors for dynamic rearrangements of the actin cytoskeleton. However, the functions of profilins in differentiated mammalian cells are uncertain because profilin deficiency is early embryonic lethal for higher eukaryotes. To examine profilin function in chondrocytes, we disrupted the profilin 1 gene in cartilage (Col2pfn1). Homozygous Col2pfn1 mice develop progressive chondrodysplasia caused by disorganization of the growth plate and defective chondrocyte cytokinesis, indicated by the appearance of binucleated cells. Surprisingly, Col2pfn1 chondrocytes assemble and contract actomyosin rings normally during cell division; however, they display defects during late cytokinesis as they frequently fail to complete abscission due to their inability to develop strong traction forces. This reduced force generation results from an impaired formation of lamellipodia, focal adhesions and stress fibres, which in part could be linked to an impaired mDia1-mediated actin filament elongation. Neither an actin nor a poly-proline binding-deficient profilin 1 is able to rescue the defects. Taken together, our results demonstrate that profilin 1 is not required for actomyosin ring formation in dividing chondrocytes but necessary to generate sufficient force for abscission during late cytokinesis.