Cilium transition zone proteome reveals compartmentalization and differential dynamics of ciliopathy complexes

Proc Natl Acad Sci U S A. 2016 Aug 30;113(35):E5135-43. doi: 10.1073/pnas.1604258113. Epub 2016 Aug 12.


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.

Keywords: BBSome; MKS/B9 complex; cilium/flagellum; transition zone; trypanosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bardet-Biedl Syndrome / genetics
  • Bardet-Biedl Syndrome / metabolism
  • Basal Bodies / metabolism
  • Basal Bodies / ultrastructure
  • Cell Compartmentation
  • Cilia / genetics
  • Cilia / metabolism*
  • Ciliary Motility Disorders / genetics
  • Ciliary Motility Disorders / metabolism
  • Ciliopathies / genetics
  • Ciliopathies / metabolism*
  • Cytoskeleton / metabolism
  • Cytoskeleton / ultrastructure
  • Encephalocele / genetics
  • Encephalocele / metabolism
  • Flagella / genetics
  • Flagella / metabolism
  • Flagella / ultrastructure
  • Humans
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Mutation
  • Polycystic Kidney Diseases / genetics
  • Polycystic Kidney Diseases / metabolism
  • Proteome / genetics
  • Proteome / metabolism*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • RNA Interference
  • Retinitis Pigmentosa
  • Trypanosoma / genetics
  • Trypanosoma / metabolism*
  • Trypanosoma / ultrastructure


  • Proteome
  • Protozoan Proteins

Supplementary concepts

  • Meckel syndrome type 1