title: Loss-of-function mutations in the human ortholog of Chlamydomonas reinhardtii ODA7 disrupt dynein arm assembly and cause primary ciliary dyskinesia.
abstract: Cilia and flagella are evolutionarily conserved structures that play various physiological roles in diverse cell types. Defects in motile cilia result in primary ciliary dyskinesia (PCD), the most prominent ciliopathy, characterized by the association of respiratory symptoms, male infertility, and, in nearly 50% of cases, situs inversus. So far, most identified disease-causing mutations involve genes encoding various ciliary components, such those belonging to the dynein arms that are essential for ciliary motion. Following a candidate-gene approach based on data from a mutant strain of the biflagellated alga Chlamydomonas reinhardtii carrying an ODA7 defect, we identified four families with a PCD phenotype characterized by the absence of both dynein arms and loss-of-function mutations in the human orthologous gene called LRRC50. Functional analyses performed in Chlamydomonas reinhardtii and in another flagellated protist, Trypanosoma brucei, support a key role for LRRC50, a member of the leucine-rich-repeat superfamily, in cytoplasmic preassembly of dynein arms.
authors: Institut National de Santé et de Recherche Médicale (INSERM) U.933, Université Pierre et Marie Curie-Paris 6 and Assistance Publique-Hôpitaux de Paris, Hôpital Armand-Trousseau, 75571 Paris cedex 12, France.
authors: Philippe
authors: P
authors: Duquesnoy
authors: Estelle
authors: E
authors: Escudier
authors: Laetitia
authors: L
authors: Vincensini
authors: Judy
authors: J
authors: Freshour
authors: Anne-Marie
authors: AM
authors: Bridoux
authors: André
authors: A
authors: Coste
authors: Antoine
authors: A
authors: Deschildre
authors: Jacques
authors: J
authors: de Blic
authors: Marie
authors: M
authors: Legendre
authors: Guy
authors: G
authors: Montantin
authors: Henrique
authors: H
authors: Tenreiro
authors: Anne-Marie
authors: AM
authors: Vojtek
authors: Céline
authors: C
authors: Loussert
authors: Annick
authors: A
authors: Clément
authors: Denise
authors: D
authors: Escalier
authors: Philippe
authors: P
authors: Bastin
authors: David R
authors: DR
authors: Mitchell
authors: Serge
authors: S
authors: Amselem
mesh_terms: D000595:Amino Acid Sequence; D016825:Chlamydomonas reinhardtii / Q000235:genetics*; D003593:Cytoplasm / Q000378:metabolism; D004252:DNA Mutational Analysis; D004398:Dyneins / Q000235:genetics*; D005260:Female; D005407:Flagella / Q000378:metabolism; D006801:Humans; D007619:Kartagener Syndrome / Q000235:genetics*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014346:Trypanosoma brucei brucei / Q000378:metabolism
chemical_list: C546358:DNAAF1 protein, human; D008869:Microtubule-Associated Proteins; D011506:Proteins; D004398:Dyneins