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Sidec > Case studies > Case studies

Novel insights into disease mechanisms

One of the main functions of the kidney is the filtration of plasma to produce urine. The size-selective kidney filter, known as the slit diaphragm (SD), prevents plasma proteins from leaking into the urine. This filtration barrier consists of layers of specialized cells (including podocytes), connected by the zipper-like structure of the SD. Defects in the SD are associated with a number of kidney diseases. The zipper-like SD structure, first described in 1974, was later questioned and the molecular nature of the SD has subsequently remained obscure.

Study objective
In a collaboration between the University of Helsinki, Karolinska Institute, University of Oulo and University of California Davis, Protein Tomography™ was used to elucidate the role of the slit diaphragm in protein filtration. Thus, a new structure for the kidney filter was described, providing valuable insights into the disease mechanisms of proteinurea.

Conclusions



Protein Tomography™ allowed a comparison between different specimens and species
The images above show a nephrin protein or a network of nephrin molecules (blue), podocyte cells (green) and gold markers (yellow) from the immunolabeling process in man, mouse, a transfected cell and a solution of recombinant nephrin protein.


Reference
Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography. Wartiovaara J, Ofverstedt LG, Khoshnoodi J, Zhang J, Makela E, Sandin S, Ruotsalainen V, Cheng RH, Jalanko H, Skoglund U, Tryggvason K. J. of Clinical Investigation. 2004, 114, 1475-1483.

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