CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs.
CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs.
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原发性纤毛运动障碍（PCD）是一种遗传性疾病，其特征在于上呼吸道和下呼吸道的复发性感染、男性生育力降低以及约50%的受影响个体的内脏逆位（Kartagener综合征）。它是由负责气道清除的呼吸道纤毛、推动精子细胞的鞭毛和决定左右不对称的结节性单纤毛的运动缺陷引起的。已经在编码外动力蛋白臂、径向辐条和轴丝动力蛋白的细胞质预组装因子的基因中鉴定了引起PCD的隐性突变，但这些突变仅占PCD病例的约50%。我们利用狗种群的独特特性定位克隆了一个新的PCD基因，CCDC39。我们发现，在人类直系同源基因的功能丧失突变的基础上的PCD案件轴丝紊乱和异常纤毛跳动的相当一部分。功能分析表明，CCDC39定位于纤毛轴丝，是必不可少的内部动力蛋白臂和动力蛋白调节复合物的组装。
Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.
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DOI：
10.1083/jcb.125.5.1109
发表时间：
1994-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Piperno G;Mead K;LeDizet M;Moscatelli A
通讯作者：
Moscatelli A
影响因子：
--
作者：
Ralston, KS;Lerner, AG;Hill, KL
通讯作者：
Hill, KL
影响因子：
3.6
作者：
Olbrich, H;Horváth, J;Omran, H
通讯作者：
Omran, H
影响因子：
7
作者：
Ge, B;Gurd, S;Pastinen, T
通讯作者：
Pastinen, T
DOI：
10.1083/jcb.200303019
发表时间：
2003-07-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Rupp G;Porter ME
通讯作者：
Porter ME