TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome

Nat Cell Biol. 2016 Jan;18(1):122-31. doi: 10.1038/ncb3273. Epub 2015 Nov 23.


The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS). However, the molecular composition and mechanisms underpinning TZ organization and barrier regulation are poorly understood. To uncover candidate TZ genes, we employed bioinformatics (coexpression and co-evolution) and identified TMEM107 as a TZ protein mutated in oral-facial-digital syndrome and JBTS patients. Mechanistic studies in Caenorhabditis elegans showed that TMEM-107 controls ciliary composition and functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking and assembly of membrane to microtubule Y-link connectors. Furthermore, nematode TMEM-107 occupies an intermediate layer of the TZ-localized MKS module by organizing recruitment of the ciliopathy proteins MKS-1, TMEM-231 (JBTS20) and JBTS-14 (TMEM237). Finally, MKS module membrane proteins are immobile and super-resolution microscopy in worms and mammalian cells reveals periodic localizations within the TZ. This work expands the MKS module of ciliopathy-causing TZ proteins associated with diffusion barrier formation and provides insight into TZ subdomain architecture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / metabolism
  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism
  • Cerebellum / abnormalities*
  • Cerebellum / metabolism
  • Cilia / metabolism*
  • Eye Abnormalities / genetics
  • Eye Abnormalities / metabolism
  • Humans
  • Kidney Diseases, Cystic / genetics
  • Kidney Diseases, Cystic / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Retina / abnormalities*
  • Retina / metabolism


  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • Tmem107 protein, mouse

Supplementary concepts

  • Agenesis of Cerebellar Vermis