Regardless of the underlying etiology, podocytes exhibit a uniform alteration in cellular morphology in pathological conditions of focal segmental glomerulosclerosis (FSGS). While one of the earliest detectable changes is characterized as a prominent retraction and simplification of the podocyte foot process network, increasing detachment of podocytes from the glomerular basement membrane is observed at later stages.
Despite significant progress, a comprehensive understanding of the adhesion-cytoskeletal nexus and its dedicated role in the pathogenesis of FSGS is lacking. Here, our overarching goal is to characterize dynamic alterations of the podocyte adhesome and to investigate their impact in the context of FSGS. For this purpose, we will combine high-resolution proteomics and multidimensional imaging approaches to describe alterations in adhesome signatures in different stages and models of FSGS. In addition, we will employ novel inducible mouse models to investigate how mechano-physical adaptation of podocytes is required to prevent podocyte detachment.