A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition

Nat Genet. 2011 Jul 3;43(8):776-84. doi: 10.1038/ng.891.


Mutations affecting ciliary components cause ciliopathies. As described here, we investigated Tectonic1 (Tctn1), a regulator of mouse Hedgehog signaling, and found that it is essential for ciliogenesis in some, but not all, tissues. Cell types that do not require Tctn1 for ciliogenesis require it to localize select membrane-associated proteins to the cilium, including Arl13b, AC3, Smoothened and Pkd2. Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a. Components of this complex co-localize at the transition zone, a region between the basal body and ciliary axoneme. Like Tctn1, loss of Tctn2, Tmem67 or Cc2d2a causes tissue-specific defects in ciliogenesis and ciliary membrane composition. Consistent with a shared function for complex components, we identified a mutation in TCTN1 that causes Joubert syndrome. Thus, a transition zone complex of Meckel and Joubert syndrome proteins regulates ciliary assembly and trafficking, suggesting that transition zone dysfunction is the cause of these ciliopathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple
  • Animals
  • Cell Membrane / physiology*
  • Cerebellar Diseases / genetics
  • Cerebellum / abnormalities
  • Chickens
  • Cilia / metabolism*
  • Cilia / pathology*
  • Ciliary Motility Disorders / genetics
  • Encephalocele / genetics
  • Eye Abnormalities / genetics
  • Humans
  • Kidney Diseases, Cystic / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphogenesis
  • Mutation / genetics*
  • Organ Specificity
  • Peptide Fragments / immunology
  • Polycystic Kidney Diseases / genetics
  • Rabbits
  • Retina / abnormalities
  • Retinitis Pigmentosa
  • Signal Transduction
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Membrane Proteins
  • Peptide Fragments
  • Tctn1 protein, human
  • Tctn1 protein, mouse
  • tectonin I
  • tectonin II

Supplementary concepts

  • Agenesis of Cerebellar Vermis
  • Meckel syndrome type 1