Work

Faculty Opinions recommendation of Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease.

Year: 2007

Type: peer-review

Abstract: Kidney podocytes and their foot processes maintain the ultrafiltration barrier and prevent urinary protein loss (proteinuria).Here we show that the GTPase dynamin is essential for podocyte function.During proteinuric kidney disease, induction of cytoplasmic cathepsin L leads to cleavage of dynamin at an evolutionary conserved site, resulting in reorganization of the podocyte actin cytoskeleton and proteinuria.Dynamin mutants that lack the cathepsin L site, or render the cathepsin L site inaccessible through dynamin self-assembly, are resistant to cathepsin L cleavage.When delivered into mice, these mutants restored podocyte function and resolve proteinuria.Our study identifies dynamin as a critical regulator of renal permselectivity that is specifically targeted by proteolysis under pathological conditions.

Source: Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

DOI: 10.3410/f.1096926.552877

Authors: David Salant, Laurence Beck

Institutions: Boston University, Boston Medical Center, Harvard University, Massachusetts General Hospital

Language: English

Topic: Renal Diseases and Glomerulopathies

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Deutscher Akademischer Austauschdienst, Albert-Ludwigs-Universität Freiburg, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases