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Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease
Open accessAbstract
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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Cited by
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Theocharis, A. D., Skandalis, S. S., Gialeli, C., & Karamanos, N. K. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.11.001 · Cited by 2,598
Faul, C., Donnelly, M., Merscher-Gomez, S., Chang, Y. H., Franz, S., Delfgaauw, J., Chang, J.-M., Choi, H. Y., Campbell, K. N., Kim, K., et al. (2008) · Nature Medicine · doi:10.1038/nm.1857 · Cited by 991
Self-citationSpecialized roles for cysteine cathepsins in health and disease
Reiser, J., Adair, B., & Reinheckel, T. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42918 · Cited by 580
Self-citationCathepsin D in Podocytes Is Important in the Pathogenesis of Proteinuria and CKD
Yamamoto-Nonaka, K., Koike, M., Asanuma, K., Takagi, M., Oliva Trejo, J. A., Seki, T., Hidaka, T., Ichimura, K., Sakai, T., Tada, N., et al. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015040366 · Cited by 59
Metadata
- Authors
- Sever, S., Altintas, M. M., Nankoe, S. R., Möller, C. C., Ko, D., Wei, C., Henderson, J., del Re, E. C., Hsing, L., Erickson, A., Cohen, C. D., Kretzler, M., Kerjaschki, D., Rudensky, A., Nikolic, B., & Reiser, J.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-08-01
- Volume
- 117
- Issue
- 8
- Pages
- 2095-2104
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2105525777
- Cited by
- 226
- References
- 0
- FWCI
- 10.15
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Sever, S., Altintas, M. M., Nankoe, S. R., Möller, C. C., Ko, D., Wei, C., Henderson, J., del Re, E. C., Hsing, L., Erickson, A., Cohen, C. D., Kretzler, M., Kerjaschki, D., Rudensky, A., Nikolic, B., & Reiser, J. (2007). Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease. Journal of Clinical Investigation. https://doi.org/10.1172/jci32022
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
