Institut National de Santé et de Recherche Médicale (INSERM) U.933, Université Pierre et Marie Curie-Paris 6 and Assistance Publique-Hôpitaux de Paris, Hôpital Armand-Trousseau, 75571 Paris cedex 12, France.
Am J Hum Genet. 2009 Dec;85(6):890-6. doi: 10.1016/j.ajhg.2009.11.008.
Cilia and flagella are evolutionarily conserved structures that play various physiological roles in diverse cell types. Defects in motile cilia result in primary ciliary dyskinesia (PCD), the most prominent ciliopathy, characterized by the association of respiratory symptoms, male infertility, and, in nearly 50% of cases, situs inversus. So far, most identified disease-causing mutations involve genes encoding various ciliary components, such those belonging to the dynein arms that are essential for ciliary motion. Following a candidate-gene approach based on data from a mutant strain of the biflagellated alga Chlamydomonas reinhardtii carrying an ODA7 defect, we identified four families with a PCD phenotype characterized by the absence of both dynein arms and loss-of-function mutations in the human orthologous gene called LRRC50. Functional analyses performed in Chlamydomonas reinhardtii and in another flagellated protist, Trypanosoma brucei, support a key role for LRRC50, a member of the leucine-rich-repeat superfamily, in cytoplasmic preassembly of dynein arms.
纤毛和鞭毛是进化上保守的结构，在不同类型的细胞中发挥着各种生理作用。运动纤毛的缺陷导致原发性纤毛运动障碍（PCD），这是最明显的纤毛病，其特征是呼吸症状、男性不育以及近 50%的病例出现 situs inversus（内脏逆位）。到目前为止，大多数鉴定出的致病突变涉及编码各种纤毛成分的基因，例如那些属于动力蛋白臂的基因，这些基因对于纤毛运动至关重要。我们根据带有 ODA7 缺陷的双鞭毛藻类衣藻突变株的数据，采用候选基因方法，鉴定了四个具有 PCD 表型的家族，其特征是缺乏动力蛋白臂和人类同源基因 LRRC50 的功能丧失突变。在衣藻和另一种鞭毛原生动物锥虫中进行的功能分析支持 LRRC50（富含亮氨酸重复超家族的成员）在动力蛋白臂的细胞质预组装中的关键作用。
