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Updated: Sep 8, 2025

Evaluation of Zebrafish Kidney Function Using a Fluorescent Clearance Assay
08:13

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Published on: February 20, 2015

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A cAMP signalosome in primary cilia drives gene expression and kidney cyst formation

Jan N Hansen1, Fabian Kaiser1, Philipp Leyendecker1

  • 1Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany.

EMBO Reports
|June 13, 2022
PubMed

Insights

Researchers discovered a distinct cAMP signalosome within primary cilia, revealing its role in kidney cyst formation. Targeting this pathway with phosphodiesterase-4 inhibitors can block cyst growth, offering new therapeutic strategies for polycystic kidney disease.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Primary cilia are crucial organelles for signal transduction, distinct from the cell body.
  • Ciliopathies, resulting from ciliary dysfunction, represent a significant group of human diseases.
  • The precise mechanisms by which ciliary signaling dictates cellular outcomes are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms of ciliary signaling.
  • To identify novel components of ciliary signalosomes.
  • To investigate the role of ciliary signaling in kidney epithelial cell function and disease.

Main Methods:

  • Spatially resolved optogenetics
  • RNA sequencing
  • High-resolution imaging

Main Results:

  • A novel cAMP signalosome, functionally separate from the cytoplasm, was identified within primary cilia.
  • Specific genes and pathways regulated by the ciliary cAMP signalosome were identified.
  • Chronic stimulation of this signalosome induced kidney epithelial-to-cyst transformation.
  • Inhibition of phosphodiesterase-4 long isoforms counteracted chronic cAMP elevation and reduced cyst growth.

Conclusions:

  • The primary cilium employs a distinct cAMP signalosome to control cellular functions and maintain tissue integrity.
  • This study reveals novel molecular players in polycystic kidney disease pathogenesis.
  • Targeting ciliary cAMP signaling offers a potential therapeutic avenue for polycystic kidney disease.
Keywords:
CREBPKDcAMPoptogeneticsprimary cilia

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