MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone

@article{Li2016MKS5AC,
  title={MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone},
  author={Chunmei Li and Victor L Jensen and Kwangjin Park and Julie E Kennedy and Francesc R. Garcia-Gonzalo and Marta Romani and Roberta De Mori and Ange-Line Bruel and Dominique Gaillard and B{\'e}r{\'e}nice Doray and Estelle Lopez and Jean-Baptiste Rivi{\`e}re and Laurence Faivre and Christel Thauvin-Robinet and Jeremy F. Reiter and Oliver E. Blacque and Enza Maria Valente and Michel R Leroux},
  journal={PLoS Biology},
  year={2016},
  volume={14}
}
Cilia have a unique diffusion barrier (“gate”) within their proximal region, termed transition zone (TZ), that compartmentalises signalling proteins within the organelle. The TZ is known to harbour two functional modules/complexes (Meckel syndrome [MKS] and Nephronophthisis [NPHP]) defined by genetic interaction, interdependent protein localisation (hierarchy), and proteomic studies. However, the composition and molecular organisation of these modules and their links to human ciliary disease… 

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TLDR
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CEP290 is essential for the initiation of ciliary transition zone assembly
TLDR
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Drosophila sensory cilia lacking MKS proteins exhibit striking defects in development but only subtle defects in adults
TLDR
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Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone
TLDR
It is shown that the ciliopathy protein Rpgrip1l governs ciliary gating by ensuring the proper amount of Cep290 at the vertebrate TZ, and the flavonoid eupatilin is identified as a potential agent to tackle ciliopathies caused by mutations in RPGRIP1L as it rescues ciliarygating in the absence of Rpg Rip1l.
Role for intraflagellar transport in building a functional transition zone
TLDR
Using the reversibility of the novel ts‐IFT‐dynein, it is shown that restoring IFT in adults (post‐developmentally) reverses defects in ciliary structure, TZ protein localisation and ciliary gating, and this ability to reverse TZ defects declines as animals age.
RPGRIP1L helps to establish the ciliary gate for entry of proteins
TLDR
A key protein of the transition zone that is needed for NPHP4 localization, helps to exclude cytoplasmic proteins from the cilia in Chlamydomonas reinhardtii.
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