Journal Article

Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins

Omran, Heymut, Zhang, Qi, Kawano, Hiroyuki, Olbrich, Heike, Mitchell, David R., Kobayashi, Daisuke, Mizuno, Hideaki, Leblond, Gerard, Miyawaki, Atsushi, Takeda, Hiroyuki, Kamiya, Ritsu, Watanabe, Yoshinori, Loges, Niki T., O’Toole, Eileen, Hara, Chikako, Zentgraf, Hanswalter, Tsukahara, Tatsuya, Hagiwara, Haruo, Reinhardt, Richard, Yagi, Toshiki, Fliegauf, Manfred, Koshida, Sumito, Seithe, Horst

2008

Overview

Cilia and flagella are highly conserved organelles that have diverse roles in cell motility and sensing extracellular signals. Motility defects in cilia and flagella often result in primary ciliary dyskinesia. However, the mechanisms underlying cilia formation and function, and in particular the cytoplasmic assembly of dyneins that power ciliary motility, are only poorly understood. Here we report a new gene, kintoun ( ktu ), involved in this cytoplasmic process. This gene was first identified in a medaka mutant, and found to be mutated in primary ciliary dyskinesia patients from two affected families as well as in the pf13 mutant of Chlamydomonas . In the absence of Ktu/PF13, both outer and inner dynein arms are missing or defective in the axoneme, leading to a loss of motility. Biochemical and immunohistochemical studies show that Ktu/PF13 is one of the long-sought proteins involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment. Cilia formation: a role for Ktu/PF13 Cilia are microtubule-rich hair-like projections on the surface of cells and are important for motility and sensory functions. Defects in cilia motility result in primary ciliary diskynesia (PCD). In this study, Takeda and colleagues, identify a novel gene, kintoun ( ktu ) important for dynein arm formation resulting in the formation of motile cilia. It is conserved from ciliated unicellular organisms to high mammals. The authors also identified mutations in the homologous gene of two human primary ciliary dyskesia families. This paper identifies a gene, kintoun ( ktu ), which is important for dynein arm formation resulting in the formation of motile cilia. It is conserved from ciliated unicellular organisms to higher mammals. Mutations in the homologous gene of two human primary ciliary dyskinesia families are also identified.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Acids / Animals / Axoneme - chemistry / Axoneme - genetics / Axoneme - metabolism / Axoneme - pathology / Biological and medical sciences / Cell research / Chlamydomonas / Chlamydomonas - genetics / Chlamydomonas - metabolism / Cilia - chemistry / Cilia - genetics / Cilia - metabolism / Cilia - pathology / Cilia and ciliary motion / Classical genetics, quantitative genetics, hybrids / Cloning, Molecular / Dynein / Dyneins - metabolism / Epithelial Cells - cytology / Fish Proteins - genetics / Fish Proteins - metabolism / Flagella (Microbiology) / Fundamental and applied biological sciences. Psychology / Gene expression / Genes / Genes, Recessive - genetics / Genetic aspects / Genetics / Genetics of eukaryotes. Biological and molecular evolution / HSP70 Heat-Shock Proteins - metabolism / Humanities and Social Sciences / Humans / Kartagener Syndrome - genetics / Kartagener Syndrome - pathology / Kidney diseases / Male / Mice / Molecular Sequence Data / multidisciplinary / Mutation / Mutation - genetics / Oryzias - embryology / Oryzias - genetics / Oryzias - metabolism / Oryzias latipes / Physiological aspects / Protein Binding / Proteins / Proteins - genetics / Proteins - metabolism / Science / Sequence Homology, Amino Acid / Sperm Motility / Testis - cytology / Vertebrata