PALLADIN · Role of palladin for actin filament organization in podocytes foot processes
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-09-01 → 2007-08-31
- EU contribution
- €148,588
- Participants
- 1
- Scheme
- EIF
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Results in brief
Final Activity Report Summary - PALLADIN (Role of palladin for actin filament organization in podocytes foot processes)
Podocytes are injured in many forms of human and experimental glomerular disease such as focal segmental glomelurosclerosis, diabetic nephropathy, and crescentic glomerulonephritis. The singularity of the actin cytoskeleton in podocytes and its critical role for podocyte function is well known. Indeed, podocytes express unique actin-associated proteins such as synaptopodin, mutation or absence of a-actinin-4 result in glomerulosclerosis, and several stimuli like polycations and mechanical stress are known to induce rapid and profound reorganization of the actin cytoskeleton in podocytes. On the basis of earlier, preliminary results we have established in this project: 1) that palladin is expressed in podocytes in the kidney; 2) that palladin associates with various other actin-associated proteins in contractile actin bundles and focal adhesions in podocytes; 3) that palladin most likely acts as a dynamic scaffolding protein in actin structures of podocytes as opposed to a stable structural role; 4) that palladin is essential for the formation of dynamic actin structures in podocytes; 5) that palladin appears to play a role in kidney disease, since it is specifically downregulated in the glomeruli of patients with focal segmental glomerulosclerosis. Further results obtained in this project suggest that palladin interacts with actin-associated proteins anchoring the podocyte slit diaphragm, and that palladin controls actin filament elongation and contractile force in podocytes via interaction with specific proteins. The results of this project have important implications for our understanding of actin filament formation and force development in foot processes in podocytes. They may open new strategies to prevent or even to reverse the loss of podocyte foot processes in kidney disease.
Data: CORDIS, © European Union
Project objective
Podocytes are injured in many forms of human and experimental glomerular disease such as focal segmental glomelurosclerosis, diabetic nephropathy, and crescentic glomerulonephritis. The singularity of the actin cytoskeleton in podocytes and its critical role for podocyte function is well known.Indeed, podocytes express unique actin-associated proteins such as synaptopodin, mutation or absence of alfa-actinin-4 result in glomerulosclerosis due to podocyte loss by unknown reasons, and several stimuli like polycations and mechanical stress are known to induce rapid and profound reorganization of the actin cytoskeleton in podocytes.Since it was shown that palladin is expressed and localized to various actin structures in podocytes, that palladin induces and is required for stress fiber formation, and that palladin is known to interact with several proteins expressed in podocytes (alfa-actinin, VASP and ezrin), it seems that palladin plays an important role for the organization of the actin cytoskeleton in podocytes.Elucidation of the role of palladin and its binding partners in podocytes as well as elucidation of its implication in renal disease will provide new insights into glomerular diseases and new perspectives in therapeutics.
Original text from CORDIS.
Participants
- ERNST MORITZ ARNDT UNIVERSITY GREIFSWALD · GREIFSWALDCoordinatorCity levelGermany
Links
Data: CORDIS, © European Union