Blaineau Christine, Tessier Magali, Dubessay Pascal, Tasse Lena, Crobu Lucien, Pagès Michel, Bastien Patrick
Laboratoire de Parasitologie-Mycologie, Biologie Moléculaire, Biologie Cellulaire et Biodiversité des Protozoaires Parasites, FRE 3013 Centre National de Recherche Scientifique/Université Montpellier I, Montpellier, France.
Curr Biol. 2007 May 1;17(9):778-82. doi: 10.1016/j.cub.2007.03.048. Epub 2007 Apr 12.
Cilia and flagella are complex, microtubule (MT)-filled cell organelles of which the structure is evolutionarily conserved from protistan cells to mammalian sperm and the size is regulated. The best-established model for flagellar length (FL) control is set by the balance of continuous MT assembly and disassembly occurring at the flagellar tip. Because steady-state assembly of tubulin onto the distal end of the flagellum requires intraflagellar transport (IFT)--a bidirectional movement of large protein complexes that occurs within the flagellum--FL control must rely upon the regulation of IFT. This does not preclude that other pathways might "directly" affect MT assembly and disassembly. Now, among the superfamily of kinesins, family-13 (MCAK/KIF2) members exhibit a MT-depolymerizing activity responsible for their essential functions in mitosis. Here we present a novel family-13 kinesin from the flagellated protozoan parasite Leishmania major, that localizes essentially to the flagellum, and whose overexpression produces flagellar shortening and knockdown yields long flagella. Using negative mutants, we demonstrate that this phenotype is linked with the MT-binding and -depolymerizing activity of this kinesin. This is the first report of an effector protein involved in FL control through a direct action in MT dynamics, thus this finding complements the assembly-disassembly model.
纤毛和鞭毛是复杂的、充满微管（MT）的细胞器，其结构从原生生物细胞到哺乳动物精子在进化上是保守的，并且大小受到调控。目前最完善的鞭毛长度（FL）控制模型是由鞭毛尖端持续发生的微管组装和拆卸之间的平衡所设定的。由于微管蛋白在鞭毛远端的稳态组装需要鞭毛内运输（IFT）——一种在鞭毛内发生的大型蛋白质复合物的双向运动——FL控制必须依赖于IFT的调节。这并不排除其他途径可能“直接”影响微管的组装和拆卸。现在，在驱动蛋白超家族中，13家族（MCAK/KIF2）成员表现出一种微管解聚活性，这与其在有丝分裂中的基本功能有关。在这里，我们展示了一种来自有鞭毛的原生动物寄生虫利什曼原虫的新型13家族驱动蛋白，它主要定位于鞭毛，其过表达会导致鞭毛缩短，而敲低则会产生长鞭毛。使用负性突变体，我们证明这种表型与这种驱动蛋白的微管结合和解聚活性有关。这是关于一种效应蛋白通过直接作用于微管动力学参与FL控制的首次报道，因此这一发现补充了组装 - 拆卸模型。
