Biomedicine

A Foothold on Renal Disease

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Science  12 Aug 2011:
Vol. 333, Issue 6044, pp. 804
DOI: 10.1126/science.333.6044.804-a
CREDIT: MELE ET AL, N. ENGL. J. MED. 365, 295 (2011); SCI. TRANSL. MED. 3, 85RA46 (2011)

Focal segmental glomerulosclerosis (FSGS) is a common kidney disorder in which many patients progress to end-stage renal disease that requires dialysis treatment. FSGS is characterized by the abnormal loss of serum proteins through the urine, caused by malfunction of the kidney's glomerular filtration barrier. Podocytes, specialized epithelial cells with foot-like processes, are key structural constituents of this filter, but how these cells help maintain the integrity of the filter is incompletely understood.

Data from two studies support the growing view that the podocyte cytoskeleton is crucial to the proper functioning of the glomerular filtration barrier and that its destabilization can cause FSGS. Mele et al. find that two families with a hereditary form of FSGS carry mutations in MYO1E, a gene coding for a nonmuscle, membrane-associated myosin in podocytes that normally colocalizes with a protein implicated in cytoskeletal remodeling; this colocalization is disrupted by the disease-causing mutations. Fornoni et al. study a drug that has shown therapeutic efficacy in FSGS and show that its beneficial activity is due to an off-target effect: stabilization of the actin cytoskeleton in podocytes.

N. Engl. J. Med. 365, 295 (2011);

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