2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2004060439v1 16/6/1693    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 Citing Articles via Google Scholar Google Scholar Articles by Gerke, P. Articles by Walz, G. Search for Related Content PubMed PubMed Citation Articles by Gerke, P. Articles by Walz, G.

NEPH2 Is Located at the Glomerular Slit Diaphragm, Interacts with Nephrin and Is Cleaved from Podocytes by Metalloproteinases

Peter Gerke^*, Lorenz Sellin, Oliver Kretz, Daniel Petraschka^*, Hanswalter Zentgraf, Thomas Benzing^* and Gerd Walz^*

^* Renal Division and Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg; Marienhospital Herne, University of Bochum, Bochum; and German Cancer Research Center, Heidelberg, Germany

Address correspondence to: Dr. Gerd Walz, Renal Division, University Hospital Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany. Phone: 49-761-270-3250; Fax: 49-761-270-3245; E-mail: walz{at}med1.ukl.uni-freiburg.de

Received for publication June 4, 2004. Accepted for publication February 26, 2005.

The NEPH family comprises three transmembrane proteins of the Ig superfamily interacting with the glomerular slit diaphragm proteins podocin and ZO-1. NEPH1 binds to nephrin, another component of the slit diaphragm, and loss of either partner causes heavy proteinuria. NEPH2, which is strongly conserved among a large number of species, is also expressed in the kidney; however, its function is unknown. The authors raised NEPH2 antisera to demonstrate NEPH2 expression in a variety of mouse tissues, including the kidney and a podocyte cell line. The authors localized the expression of NEPH2 to the glomerular slit diaphragm by electron microscopy and show NEPH2 homodimerization and specific interactions with the extracellular domain of nephrin in vitro and in vivo. NEPH1, however, failed to interact with NEPH2. The authors detected immunoreactive NEPH2 in urine of healthy subjects, suggesting that the extracellular domain is cleaved under physiologic conditions. These findings were confirmed in vitro in podocyte cell culture. Shedding is increased by tyrosine phosphatase inhibitors and diminished by GM6001, an inhibitor of metalloproteinases. Overexpression experiments indicate an involvement of the MT1-matrix metalloproteinase. The results suggest a role for NEPH2 in the organization and/or maintenance of the glomerular slit diaphragm that may differ from the functions of NEPH1 and nephrin.

This article has been cited by other articles:

				B. Hartleben, H. Schweizer, P. Lubben, M. P. Bartram, C. C. Moller, R. Herr, C. Wei, E. Neumann-Haefelin, B. Schermer, H. Zentgraf, et al. Neph-Nephrin Proteins Bind the Par3-Par6-Atypical Protein Kinase C (aPKC) Complex to Regulate Podocyte Cell Polarity J. Biol. Chem., August 22, 2008; 283(34): 23033 - 23038. [Abstract] [Full Text] [PDF]

				F. Collino, B. Bussolati, E. Gerbaudo, L. Marozio, S. Pelissetto, C. Benedetto, and G. Camussi Preeclamptic sera induce nephrin shedding from podocytes through endothelin-1 release by endothelial glomerular cells Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1185 - F1194. [Abstract] [Full Text] [PDF]

				S. E. Quaggin and J. A. Kreidberg Development of the renal glomerulus: good neighbors and good fences Development, February 15, 2008; 135(4): 609 - 620. [Abstract] [Full Text] [PDF]

				Y. Li, Y. S. Kang, C. Dai, L. P. Kiss, X. Wen, and Y. Liu Epithelial-to-Mesenchymal Transition Is a Potential Pathway Leading to Podocyte Dysfunction and Proteinuria Am. J. Pathol., February 1, 2008; 172(2): 299 - 308. [Abstract] [Full Text] [PDF]

				L. De Petris, K. A. Hruska, S. Chiechio, and H. Liapis Bone morphogenetic protein-7 delays podocyte injury due to high glucose Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3442 - 3450. [Abstract] [Full Text] [PDF]

				H. Holthofer Molecular architecture of the glomerular slit diaphragm: lessons learnt for a better understanding of disease pathogenesis Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2124 - 2128. [Full Text] [PDF]

				P. Ihalmo, H. Schmid, M. P. Rastaldi, D. Mattinzoli, R. G. Langham, P. Luimula, R. Kilpikari, M. Lassila, R. E. Gilbert, D. Kerjaschki, et al. Expression of filtrin in human glomerular diseases Nephrol. Dial. Transplant., July 1, 2007; 22(7): 1903 - 1909. [Abstract] [Full Text] [PDF]

				N. He, A. Zahirieh, Y. Mei, B. Lee, S. Senthilnathan, B. Wong, B. Mucha, F. Hildebrandt, D. E. Cole, D. Cattran, et al. Recessive NPHS2 (Podocin) Mutations Are Rare in Adult-Onset Idiopathic Focal Segmental Glomerulosclerosis Clin. J. Am. Soc. Nephrol., January 1, 2007; 2(1): 31 - 37. [Abstract] [Full Text] [PDF]

				I. Quack, L. C. Rump, P. Gerke, I. Walther, T. Vinke, O. Vonend, T. Grunwald, and L. Sellin beta-Arrestin2 mediates nephrin endocytosis and impairs slit diaphragm integrity PNAS, September 19, 2006; 103(38): 14110 - 14115. [Abstract] [Full Text] [PDF]

				C. D. Cohen, A. Klingenhoff, A. Boucherot, A. Nitsche, A. Henger, B. Brunner, H. Schmid, M. Merkle, M. A. Saleem, K.-P. Koller, et al. Comparative promoter analysis allows de novo identification of specialized cell junction-associated proteins PNAS, April 11, 2006; 103(15): 5682 - 5687. [Abstract] [Full Text] [PDF]

				K. Tryggvason, J. Patrakka, and J. Wartiovaara Hereditary proteinuria syndromes and mechanisms of proteinuria. N. Engl. J. Med., March 30, 2006; 354(13): 1387 - 1401. [Full Text] [PDF]

				R. Ma, J. Du, S. Sours, and M. Ding Store-Operated Ca2+ Channel in Renal Microcirculation and Glomeruli Experimental Biology and Medicine, February 1, 2006; 231(2): 145 - 153. [Abstract] [Full Text] [PDF]

				C. M. Meyers, M. Geanacopoulos, L. B. Holzman, and D. J. Salant Glomerular Disease Workshop J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3472 - 3476. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673