Cep164 provides a molecular link between the mother centriole and the ciliary membrane biogenesis machinery by interacting with the GEF Rabin8 and the GTPase Rab8.

The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signaling by facilitating a protein diffusion barrier at the ciliary base, and TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS) 1. However, the molecular composition and mechanisms underpinning TZ organisation and barrier regulation are poorly understood. To uncover candidate TZ genes, we employed bioinformatics (co-expression and co-evolution) and identified TMEM107 as a TZ protein mutated in oral-facial-digital syndrome (OFD) and JBTS patients. Mechanistic studies in Caenorhabditis elegans showed TMEM107 controls ciliary composition and functions redundantly with NPHP4 to regulate cilium integrity, TZ docking and assembly of membrane to microtubule Y-link connectors. Furthermore, nematode TMEM107 occupies an intermediate layer of the TZ-localised MKS module by organising recruitment of ciliopathy proteins MKS1, TMEM231 (JBTS20) and TMEM237 (JBTS14). Finally, MKS module membrane proteins are immobile and super-resolution microscopy (STED, dSTORM) in worms and mammalian cells reveals periodic localisations 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.

A functional screen identified MARK4 as a positive regulator of axonemal extension and ciliogenesis via its interaction with the mother centriolar protein ODF2.