Abstract: TH-PO1070
Linking Polarity Signaling and Mechanotransduction in Drosophila Nephrocytes
Session Information
- Glomerular Diseases: Podocyte Biology - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1204 Podocyte Biology
Authors
- Köhler, Sybille, University Hospital Cologne, Cologne, Germany
- Schermer, Bernhard, University Hospital Cologne, Cologne, Germany
- Benzing, Thomas, University of Cologne, Köln, Germany
- Denholm, Barry, Edinburgh University, Edinburgh, Edinburgh, United Kingdom
- Brinkkoetter, Paul T., University Hospital Cologne, Cologne, Germany
Background
Polarity signaling through the aPKC-Par polarity complex is essential for the development and maintenance of the podocyte architecture and the filtration function of the kidney. Despite its well-established role in aPKC-mediated signaling, neither loss of Par3A nor Par3B causes a glomerular disease phenotype. However, genetic depletion of both, Par3A and Par3B resulted in severe proteinuria and renal failure.
Methods
We utilized Drosophila nephrocytes to study the functional role of Par3 proteins in greater detail. Nephrocytes are the homolog cells of mammalian podocytes and express the Par3A/B homolog Bazooka at the nephrocyte diaphragm.
Results
Nephrocyte-specific depletion of Bazooka resulted in disturbed nephrocyte diaphragm morphology and severe filtration defects, indicating the conservation of this important pathway throughout species. To study the underlying mechanisms, we performed proteomic analysis of Bazooka-depleted nephrocytes and identified an upregulation of focal and cell adhesion proteins, actin-associated proteins and mechanosensors such as Cher (Filamin) and Rhea (Talin). The putative mechanosensor protein Filamin was identified to be upregulated upon injury in podocytes as well. As podocytes face constant mechanical stress due to blood pressure and filtration, we further investigated the functional role of the mechanosensor protein Cher in nephrocytes. Interestingly, loss of Cher did not cause morphological changes, but resulted in a significantly increased filtration function. Proteom data from Cher depleted nephrocytes revealed an upregulation of ECM associated proteins such as Viking (Col4A) and Mucin and a downregulation of proteins involved in cell adhesion processes and actin-binding.
Conclusion
Our study thereby provides the first data linking polarity signaling and mechanotransduction in nephrocytes.