Researchers from Yale University School of Medicine and University of Miami have discovered that the protein talin1 is critical to the development and maintenance of podocytes, which make up the kidney filtration barrier. They found that talin1 links integrins (the receptors that keep podocytes tightly bound to the glomerular basement membrane) to the protein actin, which makes up the internal framework of podocyte cells. Loss of talin1 in podocytes resulted in disruption of the filtration barrier, podocyte foot process effacement, defects in the actin cytoskeleton that maintains podocyte structure, proteinuria, and kidney failure. The scientists found that podocyte injury caused talin1 cleavage and ultimately, nephrotic syndrome. They determined that cleavage was brought on by increased activity of the protein calpain. When they examined urine from patients with FSGS and minimal change disease, they found an increase of calpain, similar to results in mice. Further study in animals showed that calpain inhibitors can reduce proteinuria and help keep podocytes in place. Their work highlights the importance of calpain as a potential therapeutic target and reveals insight into the development of glomerular injury and nephrotic syndrome.
Source:
Podocyte-Associated Talin1 Is Critical for Glomerular Filtration Barrier Maintenance, The Journal of Clinical Investigation, February 17, 2014