Mahjoub Moe R, Qasim Rasi M, Quarmby Lynne M
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.
Mol Biol Cell. 2004 Nov;15(11):5172-86. doi: 10.1091/mbc.e04-07-0571. Epub 2004 Sep 15.
Polycystic kidney disease and related syndromes involve dysregulation of cell proliferation in conjunction with ciliary defects. The relationship between cilia and cell cycle is enigmatic, but it may involve regulation by the NIMA-family of kinases (Neks). We previously showed that the Nek Fa2p is important for ciliary function and cell cycle in Chlamydomonas. We now show that Fa2p localizes to an important regulatory site at the proximal end of cilia in both Chlamydomonas and a mouse kidney cell line. Fa2p also is associated with the proximal end of centrioles. Its localization is dynamic during the cell cycle, following a similar pattern in both cell types. The cell cycle function of Fa2p is kinase independent, whereas its ciliary function is kinase dependent. Mice with mutations in Nek1 or Nek8 have cystic kidneys; therefore, our discovery that a member of this phylogenetic group of Nek proteins is localized to the same sites in Chlamydomonas and kidney epithelial cells suggests that Neks play conserved roles in the coordination of cilia and cell cycle progression.
多囊肾病及相关综合征涉及细胞增殖失调并伴有纤毛缺陷。纤毛与细胞周期之间的关系尚不明确,但可能涉及NIMA家族激酶(Neks)的调控。我们之前表明,Nek Fa2p对衣藻的纤毛功能和细胞周期很重要。我们现在表明,Fa2p定位于衣藻和小鼠肾细胞系中纤毛近端的一个重要调控位点。Fa2p也与中心粒的近端相关。其定位在细胞周期中是动态的,在两种细胞类型中遵循相似的模式。Fa2p的细胞周期功能不依赖激酶,而其纤毛功能依赖激酶。Nek1或Nek8发生突变的小鼠患有肾囊肿;因此,我们发现这一Nek蛋白系统发育组的一个成员定位于衣藻和肾上皮细胞的相同位点,这表明Neks在纤毛与细胞周期进程的协调中发挥保守作用。