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Emerging Mechanistic Understanding of Cilia Function in Cellular Signalling

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Date 2024 Feb 17
PMID 38366037
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Abstract

Primary cilia are solitary, immotile sensory organelles present on most cells in the body that participate broadly in human health, physiology and disease. Cilia generate a unique environment for signal transduction with tight control of protein, lipid and second messenger concentrations within a relatively small compartment, enabling reception, transmission and integration of biological information. In this Review, we discuss how cilia function as signalling hubs in cell-cell communication using three signalling pathways as examples: ciliary G-protein-coupled receptors (GPCRs), the Hedgehog (Hh) pathway and polycystin ion channels. We review how defects in these ciliary signalling pathways lead to a heterogeneous group of conditions known as 'ciliopathies', including metabolic syndromes, birth defects and polycystic kidney disease. Emerging understanding of these pathways' transduction mechanisms reveals common themes between these cilia-based signalling pathways that may apply to other pathways as well. These mechanistic insights reveal how cilia orchestrate normal and pathophysiological signalling outputs broadly throughout human biology.

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References
1.
Kinnebrew M, Luchetti G, Sircar R, Frigui S, Viti L, Naito T . Patched 1 reduces the accessibility of cholesterol in the outer leaflet of membranes. Elife. 2021; 10. PMC: 8654371. DOI: 10.7554/eLife.70504. View

2.
Ward C, Hogan M, Rossetti S, Walker D, Sneddon T, Wang X . The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nat Genet. 2002; 30(3):259-69. DOI: 10.1038/ng833. View

3.
Horst C, Forestner D, Besharse J . Cytoskeletal-membrane interactions: a stable interaction between cell surface glycoconjugates and doublet microtubules of the photoreceptor connecting cilium. J Cell Biol. 1987; 105(6 Pt 2):2973-87. PMC: 2114726. DOI: 10.1083/jcb.105.6.2973. View

4.
Su Q, Hu F, Ge X, Lei J, Yu S, Wang T . Structure of the human PKD1-PKD2 complex. Science. 2018; 361(6406). DOI: 10.1126/science.aat9819. View

5.
Wood C, Huang K, Diener D, Rosenbaum J . The cilium secretes bioactive ectosomes. Curr Biol. 2013; 23(10):906-11. PMC: 3850760. DOI: 10.1016/j.cub.2013.04.019. View