Abstract
Cell Biology A healthy human kidney filters about 180 liters of plasma per day, a highly regulated process that ensures the removal of toxins but the retention of proteins and red blood cells. Critical to this filtration process is the slit diaphragm, a cell-cell junction formed by specialized cells called podocytes that wrap around kidney capillaries. The slit diaphragm loses its structural and functional integrity in nephrotic syndrome, a disease characterized by protein loss in the urine (proteinuria) that can lead to kidney failure. Studying genetically engineered mice, Soda et al. identified a role for clathrin-mediated endocytosis, a process implicated in membrane protein recycling, in the formation and maintenance of the slit diaphragm. Podocyte-specific deletion of any of several proteins essential for endocytosis caused severe proteinuria in the mutant mice. These results suggest that the podocyte cell-cell junctions may be more dynamic than previously thought. Endocytosis could be a mechanism that allows the slit diaphragm to be rapidly remodeled in response to physiological changes such as fluctuations in blood pressure and blood volume. J. Clin. Invest. 10.1172/JCI65289 (2012).
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