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This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2009010056v1 20/7/1533    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Jones, N. Articles by Pawson, T. PubMed PubMed Citation Articles by Jones, N. Articles by Pawson, T. Related Collections Related Article

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^,||,** and Tony Pawson^,

^* Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McGill University Health Centre,, Montreal, Quebec, Canada; ^¶ Epitomics, Inc, Burlingame, California; ^|| Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; ^** Division of Nephrology, St. Michael's Hospital, Toronto, Ontario, Canada

Correspondence: Nina Jones, Ph.D, Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Room 3461, New Science Complex, Guelph, Ontario, Canada, N1G 2W1. Phone: 519-824-4120, ext. 53643; Fax: 519-837-1802; E-mail: jonesmcb{at}uoguelph.ca

Received for publication January 15, 2009. Accepted for publication March 2, 2009.

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.

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				T. Benzing The Promise of Well-Being: Stay in Shape with N(i)ck J. Am. Soc. Nephrol., July 1, 2009; 20(7): 1425 - 1427. [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673