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.
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Authors | Sanja Sever, Mehmet M Altintas, Sharif R Nankoe, Clemens C Möller, David Ko, Changli Wei, Joel Henderson, Elizabetta C del Re, Lianne Hsing, Ann Erickson, Clemens D Cohen, Matthias Kretzler, Dontscho Kerjaschki, Alexander Rudensky, Boris Nikolic, Jochen Reiser |
Journal | The Journal of clinical investigation
(J Clin Invest)
Vol. 117
Issue 8
Pg. 2095-104
(Aug 2007)
ISSN: 0021-9738 [Print] United States |
PMID | 17671649
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Actins
- Cathepsins
- Cysteine Endopeptidases
- Cathepsin L
- Ctsl protein, mouse
- Dynamins
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Topics |
- Actins
(genetics, metabolism)
- Animals
- Cathepsin L
- Cathepsins
(genetics, metabolism)
- Cells, Cultured
- Cysteine Endopeptidases
(genetics, metabolism)
- Cytoskeleton
(genetics, metabolism, pathology)
- Dynamins
(genetics, metabolism)
- Kidney Diseases
(enzymology, genetics, pathology)
- Mice
- Mutation
- Podocytes
(enzymology, pathology)
- Proteinuria
(genetics, metabolism, pathology)
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