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Emerging mechanistic understanding of cilia function in cellular signalling

Nature Reviews Molecular Cell Biology (2024)Cite this article

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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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Fig. 1: The primary cilium is a specialized compartment for signal transduction.
Fig. 2: G-protein-coupled receptor signalling in primary cilia.
Fig. 3: Hedgehog signal transduction in primary cilia.
Fig. 4: Models of polycystin function in vertebrate development and homeostasis.
Fig. 5: Crosstalk between ciliary signalling pathways.

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Authors and Affiliations

  1. Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA

    Keren I. Hilgendorf & Benjamin R. Myers

  2. Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA

    Benjamin R. Myers

  3. Department of Bioengineering, University of Utah School of Medicine, Salt Lake City, UT, USA

    Benjamin R. Myers

  4. Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA

    Jeremy F. Reiter

  5. Chan Zuckerberg Biohub, San Francisco, CA, USA

    Jeremy F. Reiter

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The authors contributed equally to all aspects of the article.

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J.F.R. consulted for Maze Therapeutics, and co-founded stealth companies funded via BridgeBio and 459AM.

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Hilgendorf, K.I., Myers, B.R. & Reiter, J.F. Emerging mechanistic understanding of cilia function in cellular signalling. Nat Rev Mol Cell Biol (2024). https://doi.org/10.1038/s41580-023-00698-5

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