Syndecan-4-dependent processing of transient receptor potential canonical type 6 (TRPC6) channels in podocytes

• Applicant: Dr. Florian Thilo
• Subject Area: Nephrology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 219576092

Podocyte dysfunction is an important cause for proteinuric kidney diseases. Genetic studies have identified transient receptor potential canonical type 6 (TRPC6) channels as important players in familial focal segmental glomerulosclerosis (FSGS) and other proteinuric diseases, however the cellular mechanisms of TRPC6 for the development of proteinuria and their regulatory factors remain poorly defined. Preliminary data show that TRPC6 expression in transfected podocytes is controlled by transmembrane heparan sulfate proteoglycan Syndecan-4 (Sdc4). In the present project, the precise role of TRPC6 in podocyte signaling and function will be investigated. It is planned to investigate TRPC6 signaling in podocytes with major focus on its role for RhoA activity, cytoskeleton rearrangement, calcium influx, membrane currents, and proteinuria. TRPC6 processing and translocation will be studied. Syndecan-4 knockout (Sdc4-/-) mice will be used to define the role of Sdc4 in these processes. These studies will advance the understanding of pathophysiologic processes underlying proteinuric kidney diseases and disease progression in chronic renal failure. The ultimate aim is to identify novel targets for the prevention and treatment of chronic kidney diseases.

• DFG Programme: Research Grants