Key Points
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There are two types of cilia, motile and non-motile primary, which have different roles in human physiology, cell signalling and development.
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Ciliopathies are human disorders that arise from the dysfunction of motile and/or non-motile cilia. At least 35 different ciliopathies collectively affect nearly all organ systems, with prevalent phenotypes including polycystic kidney disease, retinal degeneration, obesity, skeletal malformations and brain anomalies.
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There are more than 180 known ciliopathy-associated proteins, and over 240 established ciliary proteins that represent candidate ciliopathy proteins.
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The basal body, transition zone and intraflagellar transport system represent hotspots for ciliopathies.
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Proteins that do not specifically localize to cilia may influence ciliary functions and cause ciliopathies, and ciliary proteins can have extraciliary functions.
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Many complementary approaches, coupled with the sequencing of the genomes of patients, are being carried out to uncover additional ciliary proteins and their associations with known or novel ciliopathies.
Abstract
Motile and non-motile (primary) cilia are nearly ubiquitous cellular organelles. The dysfunction of cilia causes diseases known as ciliopathies. The number of reported ciliopathies (currently 35) is increasing, as is the number of established (187) and candidate (241) ciliopathy-associated genes. The characterization of ciliopathy-associated proteins and phenotypes has improved our knowledge of ciliary functions. In particular, investigating ciliopathies has helped us to understand the molecular mechanisms by which the cilium-associated basal body functions in early ciliogenesis, as well as how the transition zone functions in ciliary gating, and how intraflagellar transport enables cargo trafficking and signalling. Both basic biological and clinical studies are uncovering novel ciliopathies and the ciliary proteins involved. The assignment of these proteins to different ciliary structures, processes and ciliopathy subclasses (first order and second order) provides insights into how this versatile organelle is built, compartmentalized and functions in diverse ways that are essential for human health.
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Acknowledgements
The authors apologize for not citing numerous important studies that are relevant to this vast and growing area of biology owing to space restrictions. Funding for this work was provided by the Canadian Institutes of Health Research (CIHR; grants MOP142243 and MOP82870 to M.R.L.) and grants AR054396 and GM095941 from the NIH to J.F.R. M.R.L. acknowledges a senior scholar award from the Michael Smith Foundation for Health Research (MSFHR).
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Supplementary information
Supplementary Table S1
Human genes with established or likely roles in cilia, and links to established or potential ciliopathies (XLSX 86 kb)
Glossary
- Mother centriole
-
Centriolar structure that is remodelled into a basal body before the onset of cilium formation.
- Septins
-
Proteins that create barriers between different membrane compartments in several contexts, including possibly at the base of cilia.
- Kinesin-2
-
Heterotrimeric molecular motor that is required for the anterograde (base-to-tip) transport of the intraflagellar transport machinery.
- Dynein-2
-
Molecular motor that is involved in the retrograde (tip-to-base) transport of the intraflagellar transport machinery.
- Unfolded protein response
-
Cellular stress response caused by non-native proteins, which is specific to the endoplasmic reticulum.
- Imaginal discs
-
Collections of cells in an insect larva that develop into a specific adult structure, such as a wing or a leg.
- Exocyst complex
-
Protein complex that is involved in targeting Golgi-derived vesicles to the plasma membrane.
- Mosaicism
-
Two or more cell populations with different genotypes in a single individual.
- Centriolar satellites
-
Electron-dense puncta found at the periphery of centrosomes or basal bodies. May function as a temporary hub for several proteins that are required for the proper formation and function of cilia.
- Allelic series
-
Different mutations within a single gene that cause a range of phenotypes, from mild to more severe.
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Reiter, J., Leroux, M. Genes and molecular pathways underpinning ciliopathies. Nat Rev Mol Cell Biol 18, 533–547 (2017). https://doi.org/10.1038/nrm.2017.60
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DOI: https://doi.org/10.1038/nrm.2017.60
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