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Abstract: SA-PO197

Beclin 1 Regulates Podocyte Secretory Pathways

Session Information

  • Glomerular: Cell Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

  • 1003 Glomerular: Cell Biology

Authors

  • Bork, Tillmann, University Hospital Freiburg, Freiburg, BW, Germany
  • Liang, Wei, Renmin Hospital of Wuhan University, Wuhan, China
  • Yamahara, Kosuke, University Hospital Freiburg, Freiburg, BW, Germany
  • Huber, Tobias B., University Medical Center Hamburg, Hamburg, Germany
Background

Podocyte crosstalk with other glomerular cells might be a common theme of glomerular health and disease. However, very little is known how podocyte secretory pathways are being regulated. The complex molecular structure of the autophagy initiating protein Beclin 1 (ATG6) suggested an additional involvement in membrane dynamics. Using podocyte-specific knock-out of Beclin 1 we aimed to further elucidate the specific role of Beclin 1 in podocytes.

Methods

Mice with podocyte-specific loss of Beclin 1 were generated by using cre-loxp technique and analyzed. For autophagy assessment and primary cell culture these mice were crossed to Tomato/eGFP and GFP-LC3 reporter strains, respectively.

Results

Podocyte-specific knock-out of Beclin 1 results in proteinuria and decreased life span. Strikingly, podocytes show massively enlarged Golgi apparatus promoted by increased PI4P production leading to aberrant vesicle formation and vesicle accumulation indicating a functional disruption of the secretory pathway. In fact, VEGF secretion was massively decreased in of Beclin 1-deficient podocytes resulting in severe endothelial damage.

Conclusion

Here we identify a key regulatory protein of the secretory pathway by unravelling a novel function of Beclin 1 in podocytes. Promoting the delivery of secreted factors such as VEGF Beclin 1 is required for glomerular maintenance and might represent a novel pathway being affected in glomerular diseases.

Funding

  • Government Support - Non-U.S.