Wiese Martin, Kuhn Daniela, Grünfelder Christoph G
Parasitology Section, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
Eukaryot Cell. 2003 Aug;2(4):769-77. doi: 10.1128/EC.2.4.769-777.2003.
During its life cycle, the parasitic protozoon Leishmania mexicana differentiates from a flagellated form, the promastigote, to an amastigote form carrying a rudimentary flagellum. Besides biochemical changes, this process involves a change in overall cell morphology including flagellar shortening. A mitogen-activated protein kinase kinase homologue designated LmxMKK was identified in a homology screening and found to be critically involved in the regulation of flagellar assembly and cell size. LmxMKK is exclusively expressed in the promastigote stage and is likely to be regulated by posttranslational mechanisms such as phosphorylation. A deletion mutant for the single-copy gene revealed motile flagella dramatically reduced in length and lacking the paraflagellar rod, a structure adjacent to the axoneme in kinetoplastid flagella. Moreover, a fraction of the cells showed perturbance of the axonemal structure. Complementation of the deletion mutant with the wild-type gene restored typical promastigote morphology. We propose that LmxMKK influences anterograde intraflagellar transport to maintain flagellar length in Leishmania promastigotes; as such, it is the first protein kinase known to be involved in organellar assembly.
在其生命周期中，寄生原生动物墨西哥利什曼原虫从有鞭毛的前鞭毛体形式分化为带有退化鞭毛的无鞭毛体形式。除了生化变化外，这个过程还涉及整体细胞形态的改变，包括鞭毛缩短。在同源性筛选中鉴定出一种名为LmxMKK的丝裂原活化蛋白激酶激酶同源物，发现它在鞭毛组装和细胞大小的调节中起关键作用。LmxMKK仅在前鞭毛体阶段表达，可能受翻译后机制如磷酸化的调节。单拷贝基因的缺失突变体显示出运动鞭毛的长度显著缩短，并且缺少副鞭毛杆，这是动基体鞭毛中与轴丝相邻的一种结构。此外，一部分细胞显示出轴丝结构的紊乱。用野生型基因对缺失突变体进行互补恢复了典型的前鞭毛体形态。我们提出LmxMKK影响前向鞭毛内运输以维持利什曼原虫前鞭毛体的鞭毛长度；因此，它是已知参与细胞器组装的首个蛋白激酶。
