A Kick in the Kidneys

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Science  17 Aug 2007:
Vol. 317, Issue 5840, pp. 872
DOI: 10.1126/science.317.5840.872c

The unsurpassed filtration ability of the kidney is underpinned by the exquisite cellular architecture of the podocytes. These cells extend foot-like processes that abut the multilayered barrier of basement membrane and epithelial cells, on the other side of which lies the capillary lumen. The integrity of this barrier (which is permeable to water and small molecules), and in particular the mesh-like connections between the podocyte feet, are essential for preventing the escape of proteins into the urine (proteinuria). Sever et al. show that an intracellular GTPase, dynamin, is required for the maintenance of podocyte morphology. Dynamin contains a cleavage site for the intracellular protease cathepsin L, and in proteinuric kidney disease, cleavage leads to the rearrangement of the actin cytoskeleton in the podocytes and collapse of the feet. In a mouse model of proteinuria, introduction of a protease-resistant dynamin or a dynamin that assembled into protease-resistant higher-order structures restored podocyte function and resolved their symptoms. Dynamin has previously been implicated in endocytosis in neuronal and other cells, but a specific role in kidney anatomy was unanticipated. — SMH

J. Clin. Invest. 117, 2095 (2007).

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