title: Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella.
abstract: Intraflagellar transport (IFT) is a rapid movement of multi-subunit protein particles along flagellar microtubules and is required for assembly and maintenance of eukaryotic flagella. We cloned and sequenced a Chlamydomonas cDNA encoding the IFT88 subunit of the IFT particle and identified a Chlamydomonas insertional mutant that is missing this gene. The phenotype of this mutant is normal except for the complete absence of flagella. IFT88 is homologous to mouse and human genes called Tg737. Mice with defects in Tg737 die shortly after birth from polycystic kidney disease. We show that the primary cilia in the kidney of Tg737 mutant mice are shorter than normal. This indicates that IFT is important for primary cilia assembly in mammals. It is likely that primary cilia have an important function in the kidney and that defects in their assembly can lead to polycystic kidney disease.
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Pazour
authors.forename: B L
authors.initials: BL
authors.lastname: Dickert
authors.forename: Y
authors.initials: Y
authors.lastname: Vucica
authors.forename: E S
authors.initials: ES
authors.lastname: Seeley
authors.forename: J L
authors.initials: JL
authors.lastname: Rosenbaum
authors.forename: G B
authors.initials: GB
authors.lastname: Witman
authors.forename: D G
authors.initials: DG
authors.lastname: Cole
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002696:Chlamydomonas / Q000166:cytology / Q000235:genetics*; D002923:Cilia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D003001:Cloning, Molecular; D017124:Conserved Sequence; D005407:Flagella / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010940:Plant Proteins; D017044:Polycystic Kidney, Autosomal Recessive / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D011485:Protein Binding; D021122:Protein Subunits; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins
chemical_list: C416363:IFT88 protein, Chlamydomonas; C098623:IFT88 protein, human; D020409:Molecular Motor Proteins; D010940:Plant Proteins; D021122:Protein Subunits; D011506:Proteins; D015800:Protozoan Proteins; C490898:Tg737Rpw protein, mouse; D025521:Tumor Suppressor Proteins