Trypanosome Cell Biology Unit, Institut Pasteur & INSERM U1201, 25 rue du Docteur Roux, 75015 Paris, France; Université Pierre et Marie Curie Paris 6, Cellule Pasteur-UPMC, 25 rue du Docteur Roux, 75015 Paris, France.
Trypanosome Cell Biology Unit, Institut Pasteur & INSERM U1201, 25 rue du Docteur Roux, 75015 Paris, France.
Curr Biol. 2018 Dec 3;28(23):3802-3814.e3. doi: 10.1016/j.cub.2018.10.031. Epub 2018 Nov 15.
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 intraflagellar 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.
已经提出了几种模型来解释真核细胞如何控制纤毛和鞭毛的长度。在这里，我们研究了原生动物布氏锥虫中的这个过程，它是一种具有稳定纤毛的细胞的优秀模型系统，例如感光器或精子。我们表明，在鞭毛伸长过程中，内鞭毛运输物质（IFT，负责鞭毛构建的机械装置）的总量增加，这与前体的持续供应和先前报道的线性生长一致。通过 RNAi 敲低 IFT 驱动蛋白来降低 IFT 频率会降低伸长率，并导致较短的鞭毛组装。这些鞭毛在细胞分裂后仍继续伸长，但无法达到正常长度。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。我们提出，鞭毛在细胞分裂后被锁定，阻止进一步伸长或缩短。这一事实得到了支持，即 IFT 速率的后续增加不会导致进一步伸长。远端尖端 FLAM8 蛋白被鉴定为锁定事件的标志物。它在细胞分裂之前开始，导致子细胞中的伸长停止。在这里，我们提出了一个新的模型，称为“生长和锁定”，其中鞭毛伸长，直到以定时的方式发生锁定事件，从而固定长度。生长速度和/或锁定事件的时间的改变将导致形成不同长度的鞭毛。
