The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation
作者： Anita Becker-Heck , Irene E Zohn , Noriko Okabe , Andrew Pollock , Kari Baker Lenhart
DOI: 10.1038/NG.727
关键词: Motile cilium 、 Apical cytoplasm 、 Dynein 、 Primary ciliary dyskinesia 、 Biology 、 Kartagener Syndrome 、 Cell biology 、 Cilium 、 Ciliary Motility Disorders 、 Genetics 、 Intraflagellar transport
摘要: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with abnormal function motile cilia. Approximately half individuals PCD also have alterations in left-right organization their internal organ positioning, including situs inversus and ambiguous (Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain containing protein, CCDC40, essential for correct patterning mouse, zebrafish human. In mouse zebrafish, Ccdc40 expressed tissues that contain cilia, mutations result cilia reduced ranges motility. We further show CCDC40 humans variant misplacement central pair microtubules defective assembly inner dynein arms regulatory complexes. localizes to apical cytoplasm required axonemal recruitment CCDC39, disruption which underlies similar PCD.
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