Cardiovascular Research Institute, University of California, San Francisco, California.
Dev Dyn. 2013 Nov;242(11):1307-19. doi: 10.1002/dvdy.24024. Epub 2013 Sep 10.
Motile cilia on the inner lining of the oviductal epithelium play a central role in ovum transport toward the uterus and subsequent fertilization by sperm. While the basic ultrastructure of 9+2 motile cilia (nine peripheral microtubule doublets surrounding a central pair) has been characterized, many important steps of ciliogenesis remain poorly understood.
Our previous studies on mammalian Fused (Fu) (Stk36), a putative serine-threonine kinase, reveal a critical function of Fu in central pair construction and cilia orientation of motile cilia that line the tracheal and ependymal epithelia. These findings identify a novel regulatory component for these processes. In this study, we show that Fu is expressed in the multi-ciliated oviductal epithelium in several vertebrates, suggesting a conserved function of Fu in the oviduct. In support of this, analysis of Fu-deficient mouse oviducts uncovers a similar role of Fu in central pair construction and cilia orientation. We also demonstrate that Fu localizes to motile cilia and physically associates with kinesin Kif27 located at the cilium base and known central pair components Spag16 and Pcdp1.
Our results delineate a novel pathway for central pair apparatus assembly and add important insight to the biogenesis and function of oviductal motile cilia.
输卵管内上皮细胞的游动纤毛在卵子向子宫运输以及随后与精子受精的过程中起着核心作用。虽然已经描述了 9+2 型游动纤毛(九个外围微管二联体围绕中央对)的基本超微结构,但许多纤毛发生的重要步骤仍知之甚少。
我们之前关于哺乳动物融合蛋白(Fu)(Stk36)的研究揭示了 Fu 在中央对构建和纤毛定向中的关键作用,这些纤毛排列在气管和室管膜上皮中。这些发现确定了这些过程的一个新的调节成分。在这项研究中,我们表明 Fu 在几种脊椎动物的多纤毛输卵管上皮中表达,这表明 Fu 在输卵管中具有保守的功能。支持这一点的是,对 Fu 缺陷型小鼠输卵管的分析揭示了 Fu 在中央对构建和纤毛定向中的类似作用。我们还证明 Fu 定位于游动纤毛,并与位于纤毛基部的驱动蛋白 Kif27 以及已知的中央对成分 Spag16 和 Pcdp1 发生物理关联。
我们的结果描绘了中央对装置组装的新途径,并为输卵管游动纤毛的发生和功能提供了重要的见解。