The Role of Cdk5 in Podocyte Biology

• Applicant: Professor Dr. Paul-Thomas Brinkkötter
• Subject Area: Nephrology
• Term: from 2011 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 198523828

Glomerular diseases are a leading cause of chronic and end stage kidney failure. The terminally differentiated and highly specialized glomerular epithelial cell, the podocyte, is a critical component of the glomerular filtration barrier, and required for normal glomerular integrity. Loss of podocytes due to apoptosis and detachment of the cells from the glomerular basement membrane (GBM) contributes to the development of kidney diseases resulting in proteinuria and glomerulosclerosis. Thus, understanding regulatory mechanisms ascertaining podocyte function and survival is of major importance. We have shown that both, p35 and cyclin I mediated cyclin dependent kinase (Cdk) 5 activity is crucial for podocyte survival following acquired injury. Cdk5 is an atypical Cdk that is not involved in cell cycle regulation but rather controls cellular differentiation. In this project we will (i) investigate how Cdk5 regulates glomerular biology, (ii) identify components of the Cdk5 pathway and characterize regulatory principles of the signalling network involved and (iii) unravel the role of atypical cyclin-dependent kinases in the pathogenesis of renal diseases. We expect that our results will lead to a better understanding of a large group of glomerular disorders that is characterized by the development of proteinuria and kidney failure.

• DFG Programme: Research Grants