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Cellular signalling by primary cilia in development, organ function and disease.

Zeinab Anvarian1, Kirk Mykytyn2, Saikat Mukhopadhyay3

  • 1Department of Biology, Section of Cell Biology and Physiology, University of Copenhagen, Copenhagen, Denmark.

Nature Reviews. Nephrology
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Primary cilia act as cellular sensors, coordinating crucial signaling pathways like Hedgehog (HH) for development and homeostasis. Defects in these cilia cause ciliopathies, highlighting their importance in health and disease.

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • Primary cilia are essential cellular antennae involved in sensing extracellular cues.
  • Their function relies on precise protein localization and trafficking within the cilium.
  • Dysfunctional cilia lead to a range of human diseases known as ciliopathies.

Purpose of the Study:

  • To review the central mechanisms of primary cilia in coordinating key signaling pathways.
  • To illustrate the link between ciliary signaling defects and developmental disorders.

Main Methods:

  • Literature review of primary cilia function and signaling pathways.
  • Analysis of existing evidence on receptor localization and temporal changes in cilia.
  • Synthesis of data linking ciliary dysfunction to disease.

Main Results:

  • Primary cilia coordinate Hedgehog (HH), G protein-coupled receptor, WNT, receptor tyrosine kinase, and TGFβ/BMP signaling.
  • Receptor and signaling module localization within cilia is dynamic and cell-type specific.
  • Mutations affecting cilia cause diverse ciliopathies.

Conclusions:

  • Primary cilia are critical hubs for integrating multiple signaling pathways.
  • Aberrant ciliary signaling underlies various developmental disorders and disease progression.
  • Understanding ciliary mechanisms is key to addressing ciliopathies.