CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms  

Oleh:

Panizzi, Jennifer R ; Becker-Heck, Anita ; Castleman, Victoria H

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Genetics vol. 44 no. 06 (Jun. 2012), page 714–719.

Ketersediaan

Perpustakaan FK Nomor Panggil: N12.K.2012.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation and establishing laterality1. Cilia motility defects cause primary ciliary dyskinesia (PCD, MIM244400), a disorder affecting 1:15,000–30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive ciliary bending2. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD-linked loci3. Here we show that the zebrafish cilia paralysis mutant schmalhans (smhtn222) encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a-regulated gene product. Screening 146 unrelated PCD families identified individuals in six families with reduced outer dynein arms who carried mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103/Pr46b functions as a tightly bound, axoneme-associated protein. These results identify Ccdc103 as a dynein arm attachment factor that causes primary ciliary dyskinesia when mutated.

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