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A tale of two tails: ciliary mechanotransduction in ADPKD

Horacio F Cantiello1

  • 1Renal Unit, Massachusetts General Hospital East, 149 13th Street, Charlestown, MA 02129, USA. cantiello@helix.mgh.harvard.edu

Trends in Molecular Medicine
|June 28, 2003
PubMed

Insights

Autosomal dominant polycystic kidney disease (ADPKD) arises from mutations in PKD1/PKD2 genes. Cilia bending activates the polycystin complex, crucial for calcium signaling in kidney development.

Area of Science:

  • Nephrology
  • Genetics
  • Cell Biology

Background:

  • Autosomal dominant polycystic kidney disease (ADPKD) is a common, lethal genetic disorder.
  • It involves cyst development in kidneys, pancreas, and liver, along with cardiovascular anomalies.
  • Mutations in PKD1 and PKD2 genes, encoding polycystin-1 (PC1) and polycystin-2 (PC2), cause nearly all ADPKD cases.

Purpose of the Study:

  • To elucidate the mechanisms linking PKD1/PKD2 mutations to aberrant kidney development in ADPKD.
  • To investigate the role of primary cilia and the PC1-PC2 channel complex in ADPKD pathogenesis.

Main Methods:

  • Focus on primary cilia as sensory transducers in renal epithelial cells.
  • Analysis of the PC1-PC2 channel complex activation by mechanosensitive signals (cilia bending).

Main Results:

  • Cilia bending activates the PC1-PC2 channel complex.
  • A functional PC1-PC2 complex mediates transient calcium (Ca2+) influx.
  • This influx is coupled to intracellular calcium release.

Conclusions:

  • Abnormalities in the PC1-PC2 channel complex, potentially due to PKD1/PKD2 mutations, disrupt normal calcium signaling.
  • Dysfunctional cilia-mediated mechanotransduction is implicated in ADPKD development.
  • Understanding these mechanisms offers potential therapeutic targets for ADPKD.

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