Ablation of the single dynamin of T-brucei blocks mitochondrial fission and endocytosis and leads to a precise cytokinesis arrest
Ablation of the single dynamin of T-brucei blocks mitochondrial fission and endocytosis and leads to a precise cytokinesis arrest
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DOI：
10.1242/jcs.03023
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发表时间：
2006-07-15
影响因子：
4
通讯作者：
Schneider, Andre
中科院分区：
文献类型：
--
作者：
Chanez, Anne-Laure;Hehl, Adrian B.;Schneider, Andre
线粒体的分裂是由动力蛋白样蛋白(DLP)介导的。布氏锥虫含有单一的DLP，是动力素超家族中唯一的成员。我们之前已经证明，人促凋亡基因Bax在布鲁氏锥虫中的表达会导致广泛的线粒体碎裂。在这里，我们报告Bax诱导的线粒体分裂在缺乏功能性DLP的细胞系中被取消，这表明该蛋白在细胞周期中也是线粒体分裂所必需的。此外，DLP消融的细胞缺乏内吞作用，因此积累了增大的鞭毛袋。因此，除了在线粒体分裂中的预期作用外，锥虫DLP还需要内吞作用，这一功能被认为仅限于经典的动力素。与其双重功能一致，DLP定位于线粒体和鞭毛袋，即发生内吞作用的部位。出乎意料的是，DLP的消融也会导致胞质分裂停止。事实上，在受阻的细胞中没有观察到多核现象，这一事实证明了细胞周期的精确阻断。此外，对笼蛋白基因敲除细胞系的分析表明，胞质分裂停滞不是由于内吞缺陷造成的。因此，我们的结果支持一个工作模型，即线粒体分裂触发细胞质分裂的检查点。
Mitochondrial fission is mediated by dynamin-like proteins (DLPs). Trypanosoma brucei contains a single DLP, which is the only member of the dynamin superfamily. We have previously shown that expression of the human proapoptotic Bax in T. brucei induces extensive mitochondrial fragmentation. Here we report that Bax-induced mitochondrial fission is abolished in cell lines lacking functional DLP suggesting that the protein is also required for mitochondrial division during the cell cycle. Furthermore, DLP-ablated cells are deficient for endocytosis and as a consequence accumulate enlarged flagellar pockets. Thus, besides its expected role in mitochondrial fission the trypanosomal DLP is required for endocytosis, a function thought to be restricted to classical dynamins. In agreement with its dual function, the DLP localizes to both the mitochondrion and the flagellar pocket, the site where endocytosis occurs. Unexpectedly, ablation of DLP also causes an arrest of cytokinesis. The fact that no multinucleation is observed in the arrested cells argues for a precise cell-cycle block. Furthermore, analysis of a clathrin-knockdown cell line suggests that the cytokinesis arrest is not due to the endocytosis defect. Thus, our results support a working model in which mitochondrial fission triggers a checkpoint for cytokinesis.