Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes

Katsuhiko Asanuma, Kirk Nicholas Campbell, Kwanghee Kim, Christian H Faul, Peter Mundel

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Kidney podocytes and their slit diaphragms (SDs) form the final barrier to urinary protein loss. There is mounting evidence that SD proteins also participate in intracellular signaling pathways. The SD protein nephrin serves as a component of a signaling complex that directly links podocyte junctional integrity to actin cytoskeletal dynamics. Another SD protein, CD2-associated protein (CD2AP), is an adaptor molecule involved in podocyte homeostasis that can repress proapoptotic TGF-β signaling in podocytes. Here we show that dendrin, a protein originally identified in telencephalic dendrites, is a constituent of the SD complex, where it directly binds to nephrin and CD2AP. In experimental glomerulonephritis, dendrin relocates from the SD to the nucleus of injured podocytes. High-dose, proapoptotic TGF-β1 directly promotes the nuclear import of dendrin, and nuclear dendrin enhances both staurosporine- and TGF-β1-mediated apoptosis. In summary, our results identify dendrin as an SD protein with proapoptotic signaling properties that accumulates in the podocyte nucleus in response to glomerular injury and provides a molecular target to tackle proteinuric kidney diseases. Nuclear relocation of dendrin may provide a mechanism whereby changes in SD integrity could translate into alterations of podocyte survival under pathological conditions.

Original languageEnglish
Pages (from-to)10134-10139
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number24
DOIs
StatePublished - Jun 12 2007
Externally publishedYes

Fingerprint

Podocytes
Diaphragm
Protein Binding
Carrier Proteins
Apoptosis
Proteins
Telencephalon
Staurosporine
Cell Nucleus Active Transport
nephrin
dendrin
CD2-associated protein
Kidney Diseases
Glomerulonephritis
Dendrites
Actins
Homeostasis
Kidney
Wounds and Injuries

Keywords

  • Glomerular injury
  • Proapoptotic signaling
  • Slit diaphragm
  • TGF-β signaling

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes. / Asanuma, Katsuhiko; Campbell, Kirk Nicholas; Kim, Kwanghee; Faul, Christian H; Mundel, Peter.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 24, 12.06.2007, p. 10134-10139.

Research output: Contribution to journalArticle

Asanuma, Katsuhiko ; Campbell, Kirk Nicholas ; Kim, Kwanghee ; Faul, Christian H ; Mundel, Peter. / Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 24. pp. 10134-10139.
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