A Grow-and-Lock Model for the Control of Flagellum Length in Trypanosomes
A Grow-and-Lock Model for the Control of Flagellum Length in Trypanosomes
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DOI：
10.1016/j.cub.2018.10.031
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发表时间：
2018-12-03
期刊：
影响因子：
9.2
通讯作者：
Bastin, Philippe
中科院分区：
文献类型：
--
作者：
Bertiaux, Eloise;Morga, Benjamin;Bastin, Philippe
已经提出了几个模型来解释真核细胞如何控制其纤毛和鞭毛的长度。在这里，我们在原生布鲁氏锥虫中研究了这一过程，这是一个具有稳定纤毛的细胞（如光感受器或精子）的优秀模型系统。我们发现鞭毛内运输物质（IFT，负责鞭毛构建的机械）的总量在鞭毛伸长期间增加，与前体的持续输送和先前报道的线性增长一致。通过RNAi敲低IFT驱动马达来降低IFT频率会减慢延伸率并导致更短的鞭毛组装。它们在细胞分裂后继续伸长，但不能达到正常长度。这种失败既不是由于缺乏前体，也不是由于细胞体的形态发生控制。我们认为鞭毛在细胞分裂后被锁定，防止进一步伸长或缩短。这一点得到了以下事实的支持：随后IFT速率的增加不会导致进一步的伸长。末端的FLAM8蛋白被确定为锁定事件的标记物。它是在细胞分裂之前开始的，导致子细胞伸长的停止。在这里，我们提出了一种称为“生长和锁定”的新模型，其中鞭毛伸长，直到锁定事件以及时定义的方式发生，从而固定长度。生长速率和/或锁定事件发生时间的改变会导致形成不同长度的鞭毛。
Several models have been proposed to explain how eukaryotic cells control the length of their cilia and flagella. Here, we investigated this process in the protist Trypanosoma brucei, an excellent model system for cells with stable cilia like photoreceptors or spermatozoa. We show that the total amount of intra-flagellar transport material (IFT, the machinery responsible for flagellum construction) increases during flagellum elongation, consistent with constant delivery of precursors and the previously reported linear growth. Reducing the IFT frequency by RNAi knockdown of the IFT kinesin motors slows down the elongation rate and results in the assembly of shorter flagella. These keep on elongating after cell division but fail to reach the normal length. This failure is neither due to an absence of precursors nor to a morphogenetic control by the cell body. We propose that the flagellum is locked after cell division, preventing further elongation or shortening. This is supported by the fact that subsequent increase in the IFT rate does not lead to further elongation. The distal tip FLAM8 protein was identified as a marker for the locking event. It is initiated prior to cell division, leading to an arrest of elongation in the daughter cell. Here, we propose a new model termed "grow and lock" where the flagellum elongates until a locking event takes place in a timely defined manner, hence fixing length. Alteration in the growth rate and/ or in the timing of the locking event would lead to the formation of flagella of different lengths.