title: Cilium transition zone proteome reveals compartmentalization and differential dynamics of ciliopathy complexes.
abstract: The transition zone (TZ) of eukaryotic cilia and flagella is a structural intermediate between the basal body and the axoneme that regulates ciliary traffic. Mutations in genes encoding TZ proteins (TZPs) cause human inherited diseases (ciliopathies). Here, we use the trypanosome to identify TZ components and localize them to TZ subdomains, showing that the Bardet-Biedl syndrome complex (BBSome) is more distal in the TZ than the Meckel syndrome (MKS) complex. Several of the TZPs identified here have human orthologs. Functional analysis shows essential roles for TZPs in motility, in building the axoneme central pair apparatus and in flagellum biogenesis. Analysis using RNAi and HaloTag fusion protein approaches reveals that most TZPs (including the MKS ciliopathy complex) show long-term stable association with the TZ, whereas the BBSome is dynamic. We propose that some Bardet-Biedl syndrome and MKS pleiotropy may be caused by mutations that impact TZP complex dynamics.
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; samuel.dean@path.ox.ac.uk keith.gull@path.ox.ac.uk.
authors: Samuel
authors: 0000-0002-4792-2198
authors: S
authors: Dean
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
authors: Flavia
authors: F
authors: Moreira-Leite
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 142 20 Prague 4, Czech Republic.
authors: Vladimir
authors: V
authors: Varga
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; samuel.dean@path.ox.ac.uk keith.gull@path.ox.ac.uk.
authors: Keith
authors: K
authors: Gull
mesh_terms: D020788:Bardet-Biedl Syndrome / Q000235:genetics / Q000378:metabolism; D064652:Basal Bodies / Q000378:metabolism / Q000648:ultrastructure; D002451:Cell Compartmentation; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D002925:Ciliary Motility Disorders / Q000235:genetics / Q000378:metabolism; D000072661:Ciliopathies / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004677:Encephalocele / Q000235:genetics / Q000378:metabolism; D005407:Flagella / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009154:Mutation; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012174:Retinitis Pigmentosa; D014345:Trypanosoma / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D020543:Proteome; D015800:Protozoan Proteins
keywords: BBSome; MKS/B9 complex; cilium/flagellum; transition zone; trypanosome