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Abstract: FR-PO710

The Mechanosensitive Ion Channel Piezo Activates Rho1 in Drosophila Nephrocytes

Session Information

Category: Glomerular Diseases

  • 1304 Glomerular Diseases: Podocyte Biology


  • Koehler, Sybille, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Lindenmeyer, Maja, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Huber, Tobias B., University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Denholm, Barry, Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom

Podocytes constantly face biomechanical forces such as shear stress and hydrostatic pressure. Increasing forces result in morphological changes, detachment from the glomerular basement membrane and loss into the primary urine. This highlights a requirement for podocytes to sense changes in their physical environment and induce a response to react to increased biomechanical force.


Here, we investigated the functional role of the mechano-sensitive ion channel Piezo in Drosophila nephrocytes.


First, we confirmed Piezo expression and localisation at the nephrocyte diaphragm. Acute activation of the channel with the chemical compound YODA revealed significantly increased Ca++ signalling and Rho1 activation, suggesting a functional role of Piezo in nephrocytes and delineating the putative Piezo mechanosensitive pathway.
For further analysis, we used knockout flies and observed a filtration phenotype, while morphology and GTPase activation was not altered. In addition, we also studied the impact of elevated Piezo levels and could show, that in line with the YODA effect, Piezo overexpression revealed severely increased Rho1-GTP levels and FITC uptake, while morphology was not changed. Because of this severe pathological phenotype, we tried to rescue the effects of Piezo overexpression with pharmacological inhibition by using tarantula toxin. Intriguingly, treatment with tarantula toxin reversed the elevated Rho1-GTP levels observed upon Piezo overexpression.
Moreover, we were able to confirm Piezo1 and Piezo2 expression in mammalian podocytes and observed an upregulation of Piezo2 in glomerular disease tissue including Lupus, FSGS and hypertension.


Taken together, our data confirms the functional expression of Piezo in nephrocytes, its role in regulating GTPases and the beneficial effect of tarantula toxin to reverse the pathological effects caused by increased Piezo levels.