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Abstract: SA-PO212

The Role of the Atypical Cyclin-Dependent Kinase Cdk5 on Development and Function of Podocytes

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


  • Mangold, Nicole C., University of Cologne, Köln, Germany
  • Hagmann, Henning, University Hospital Cologne, Cologne, Germany
  • Shankland, Stuart J., University of Washington, Seattle, Washington, United States
  • Rinschen, Markus M., CECAD, Cologne, Germany
  • Benzing, Thomas, University of Cologne, Köln, Germany
  • Brinkkoetter, Paul T., University Hospital Cologne, Cologne, Germany

The atypical Cyclin-dependent kinase 5 (Cdk5) controls migration, cell adhesion and synaptic plasticity in neurons. In the kidney Cdk5 expression is restricted to the podocytes. In these visceral epithelial cells Cdk5 is activated by three known activators, p35, p25 and Cyclin I and mediates anti-apoptotic function via MEK/ERK and BCL-2. This led to the hypothesis, that Cdk5 is a master regulator of podocyte apoptosis or detachment from the glomerular basement membrane. In the mouse model of nephrotoxic nephritis the conventional knockout of Cyclin I and p35 as well as the conventional double knockout of these alleles were shown to cause increase susceptibility to glomerular damage. Prolonged and mislocalized activity of Cdk5 by increased levels of p25 in neurons leads to neurodegeneration phenotypes and dementia.


To evaluate the role of the Cdk5 effector kinase in podocytes, podocyte specific Cdk5 knockout mice were generated by crossing Cdk5 floxed mice to a podocyte-specific Podocin:Cre line. Mice were born according to Mendelian rules and did not develop a phenotype until the age of 72 weeks as documented in urine and serum analyses as well as immunohistochemical stainings. In the nephrotoxic nephritis model Cdk5-deficiency resulted in increased susceptibility to glomerular injury, aggravated proteinuria and glomerular sclerosis and a decreased number of podocytes per glomerulum.
In addition, a transgenic podocyte cell line expressing MYC-tagged p25 was generated by lentiviral gene transfer to investigate Cdk5 hyperactivity in podocytes. As compared to control podocytes, p25-transgenic cells showed an enhanced migratory phenotype, survival was not affected. Proteomic using MS/MS analysis revealed enhanced expression of proteins modulating cytoskeletal remodeling.


Whereas Cdk5 deficient mice develop no phenotype at baseline, this study highlights the anti-apoptotic effect of Cdk5 in the model of nephrotoxic nephritis. Whether activity of Cdk5 is protective in disease most likely depends on the balance of specific Cdk5-activators in the cell.


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