title: CFAP54 is required for proper ciliary motility and assembly of the central pair apparatus in mice.
abstract: Motile cilia and flagella play critical roles in fluid clearance and cell motility, and dysfunction commonly results in the pediatric syndrome primary ciliary dyskinesia (PCD). CFAP221, also known as PCDP1, is required for ciliary and flagellar function in mice and Chlamydomonas reinhardtii, where it localizes to the C1d projection of the central microtubule apparatus and functions in a complex that regulates flagellar motility in a calcium-dependent manner. We demonstrate that the genes encoding the mouse homologues of the other C. reinhardtii C1d complex members are primarily expressed in motile ciliated tissues, suggesting a conserved function in mammalian motile cilia. The requirement for one of these C1d complex members, CFAP54, was identified in a mouse line with a gene-trapped allele. Homozygous mice have PCD characterized by hydrocephalus, male infertility, and mucus accumulation. The infertility results from defects in spermatogenesis. Motile cilia have a structural defect in the C1d projection, indicating that the C1d assembly mechanism requires CFAP54. This structural defect results in decreased ciliary beat frequency and perturbed cilia-driven flow. This study identifies a critical role for CFAP54 in proper assembly and function of mammalian cilia and flagella and establishes the gene-trapped allele as a new model of PCD.
authors.affiliation: Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104.
authors.forename: Casey W
authors.initials: CW
authors.lastname: McKenzie
authors.affiliation: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655.
authors.forename: Branch
authors.initials: B
authors.lastname: Craige
authors.affiliation: Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104.
authors.forename: Tiffany V
authors.initials: TV
authors.lastname: Kroeger
authors.affiliation: Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104.
authors.forename: Rozzy
authors.initials: R
authors.lastname: Finn
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Wyatt
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Sisson
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Pavlik
authors.affiliation: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655.
authors.forename: Lara
authors.initials: L
authors.lastname: Strittmatter
authors.affiliation: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Hendricks
authors.affiliation: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655.
authors.forename: George B
authors.initials: GB
authors.lastname: Witman
authors.affiliation: Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104 Department of Pediatrics, Sanford School of Medicine of the University of South Dakota, Sioux Falls, SD 57105 Lance.Lee@sanfordhealth.org.
authors.forename: Lance
authors.initials: L
authors.lastname: Lee
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D016825:Chlamydomonas reinhardtii / Q000378:metabolism; D002923:Cilia / Q000378:metabolism / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005407:Flagella / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D007248:Infertility, Male / Q000235:genetics; D007619:Kartagener Syndrome; D008297:Male; D051379:Mice; D008870:Microtubules / Q000235:genetics; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013091:Spermatogenesis / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; C527281:Pcdp1 protein, mouse; D011506:Proteins