The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation.
The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation.
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原发性纤毛运动障碍（PCD）是一种遗传异质性常染色体隐性遗传疾病，其特征是与运动纤毛功能异常相关的呼吸道反复感染。大约一半的PCD患者还具有内脏器官定位的左右组织的改变，包括内脏逆位和内脏模糊位（Kartagener综合征，KS）。在这里，我们确定了一个未知的卷曲螺旋结构域包含蛋白质（CCDC40）的正确的左右图案在小鼠，斑马鱼和人类。Ccdc40在含有运动纤毛的组织中表达，Ccdc40的突变导致纤毛运动范围降低。重要的是，我们证明了CCDC40缺陷导致一种新的PCD变体，其特征在于中心对微管的错位和内部动力蛋白臂（IDAs）和动力蛋白调节复合物（DRCs）的轴丝组装缺陷。CCDC40定位于运动纤毛和顶端细胞质，并负责CCDC39的轴丝募集，CCDC39也在类似的PCD变体中突变。
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with abnormal function of motile cilia. Approximately half of PCD patients also have alterations in the left-right organization of internal organ positioning including situs inversus and situs ambiguous (Kartagener’s Syndrome, KS). Here we identify an uncharacterized coiled-coil domain containing protein (CCDC40) essential for correct left-right patterning in mouse, zebrafish and humans. Ccdc40 is expressed in tissues that contain motile cilia and mutation of Ccdc40 results in cilia with reduced ranges of motility. Importantly, we demonstrate that CCDC40 deficiency causes a novel PCD variant characterized by misplacement of central pair microtubules and defective axonemal assembly of inner dynein arms (IDAs) and dynein regulator complexes (DRCs). CCDC40 localizes to motile cilia and the apical cytoplasm and is responsible for axonemal recruitment of CCDC39, which is also mutated in a similar PCD variant.
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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：
2.6
作者：
Liu, AM;Joyner, AL;Turnbull, DH
通讯作者：
Turnbull, DH
影响因子：
64.8
作者：
Omran, Heymut;Kobayashi, Daisuke;Olbrich, Heike;Tsukahara, Tatsuya;Loges, Niki T.;Hagiwara, Haruo;Zhang, Qi;Leblond, Gerard;O'Toole, Eileen;Hara, Chikako;Mizuno, Hideaki;Kawano, Hiroyuki;Fliegauf, Manfred;Yagi, Toshiki;Koshida, Sumito;Miyawaki, Atsushi;Zentgraf, Hanswalter;Seithe, Horst;Reinhardt, Richard;Watanabe, Yoshinori;Kamiya, Ritsu;Mitchell, David R.;Takeda, Hiroyuki
通讯作者：
Takeda, Hiroyuki
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
2.5
作者：
Holmes, G;Niswander, L
通讯作者：
Niswander, L