Nck proteins maintain the adult glomerular filtration barrier

Nina Jones*, Laura A. New, Megan A. Fortino, Vera Eremina, Julie Ruston, Ivan M. Blasutig, Lamine Aoudjit, Youling Zou, Xiuwen Liu, Guo Liang Yu, Tomoko Takano, Susan E. Quaggin, Tony Pawson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Within the glomerulus, the scaffolding protein nephrin bridges the actin-rich foot processes that extend from adjacent podocytes to form the slit diaphragm. Mutations affecting a number of slit diaphragm proteins, including nephrin, cause glomerular disease through rearrangement of the actin cytoskeleton and disruption of the filtration barrier. We recently established that the Nck family of Src homology 2 (SH2)/SH3 cytoskeletal adaptor proteins can mediate nephrin-dependent actin reorganization. Formation of foot processes requires expression of Nck in developing podocytes, but it is unknown whether Nck maintains podocyte structure and function throughout life. Here, we used an inducible transgenic strategy to delete Nck expression in adult mouse podocytes and found that loss of Nck expression rapidly led to proteinuria, glomerulosclerosis, and altered morphology of foot processes. We also found that podocyte injury reduced phosphorylation of nephrin in adult kidneys. These data suggest that Nck is required to maintain adult podocytes and that phosphotyrosine-based interactions with nephrin may occur in foot processes of resting, mature podocytes.

Original languageEnglish (US)
Pages (from-to)1533-1543
Number of pages11
JournalJournal of the American Society of Nephrology
Issue number7
StatePublished - Jul 2009

ASJC Scopus subject areas

  • Nephrology


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