help button home button Am J Pathol ASIP MEMBERSHIP
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Khoshnoodi, J.
Right arrow Articles by Tryggvason, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Khoshnoodi, J.
Right arrow Articles by Tryggvason, K.
(American Journal of Pathology. 2003;163:2337-2346.)
© 2003 American Society for Investigative Pathology

Nephrin Promotes Cell-Cell Adhesion through Homophilic Interactions

Jamshid Khoshnoodi*, Kristmundur Sigmundsson{dagger}, Lars-Göran Öfverstedt{dagger}, Ulf Skoglund{dagger}, Björn Öbrink{dagger}, Jorma Wartiovaara{ddagger} and Karl Tryggvason*

From the Departments of Medical Biochemistry and Biophysics* and Cell and Molecular Biology,{dagger} Karolinska Institutet, Stockholm, Sweden; and the Institute of Biotechnology,{ddagger} University of Helsinki, Helsinki, Finland

Nephrin is a type-1 transmembrane protein and a key component of the podocyte slit diaphragm, the ultimate glomerular plasma filter. Genetic and acquired diseases affecting expression or function of nephrin lead to severe proteinuria and distortion or absence of the slit diaphragm. Here, we showed by using a surface plasmon resonance biosensor that soluble recombinant variants of nephrin, containing the extracellular part of the protein, interact with each other in a specific and concentration-dependent manner. This molecular interaction was increased by twofold in the presence of physiological Ca2+concentration, indicating that the binding is not dependent on, but rather promoted by Ca2+. Furthermore, transfected HEK293 cells and an immortalized mouse podocyte cell line overexpressing full-length human nephrin formed cellular aggregates, with cell-cell contacts staining strongly for nephrin. The distance between plasma membranes at the nephrin-containing contact sites was shown by electron microscopy to be 40 to 50 nm, similar to the width of glomerular slit diaphragm. The cell contacts could be dissociated with antibodies reacting with the first two extracellular Ig-like domains of nephrin. Wild-type HEK293 cells were shown to express slit diaphragm components CD2AP, P-cadherin, FAT, and NEPH1. The results show that nephrin molecules exhibit homophilic interactions that could promote cellular contacts through direct nephrin-nephrin interactions, and that the other slit diaphragm components expressed could contribute to that interaction.




This article has been cited by other articles:


Home page
 DevelopmentHome page
S. Zhuang, H. Shao, F. Guo, R. Trimble, E. Pearce, and S. M. Abmayr
Sns and Kirre, the Drosophila orthologs of Nephrin and Neph1, direct adhesion, fusion and formation of a slit diaphragm-like structure in insect nephrocytes
Development, July 15, 2009; 136(14): 2335 - 2344.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
S. F. Heeringa, C. N. Vlangos, G. Chernin, B. Hinkes, R. Gbadegesin, J. Liu, B. E. Hoskins, F. Ozaltin, F. Hildebrandt, and Members of the APN Study Group
Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndrome
Nephrol. Dial. Transplant., November 1, 2008; 23(11): 3527 - 3533.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
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]

Home page
 Mol. Cell. Biol.Home page
P. Garg, R. Verma, D. Nihalani, D. B. Johnstone, and L. B. Holzman
Neph1 Cooperates with Nephrin To Transduce a Signal That Induces Actin Polymerization
Mol. Cell. Biol., December 15, 2007; 27(24): 8698 - 8712.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
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]

Home page
 FASEB J.Home page
L. Kaufman, G. Yang, K. Hayashi, J. R. Ashby, L. Huang, M. J. Ross, M. E. Klotman, and P. E. Klotman
The homophilic adhesion molecule sidekick-1 contributes to augmented podocyte aggregation in HIV-associated nephropathy
FASEB J, May 1, 2007; 21(7): 1367 - 1375.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
K.-W. Lai, C.-L. Wei, L.-K. Tan, P.-H. Tan, G. S.C. Chiang, C. G.L. Lee, S. C. Jordan, and H.-K. Yap
Overexpression of Interleukin-13 Induces Minimal-Change-Like Nephropathy in Rats
J. Am. Soc. Nephrol., May 1, 2007; 18(5): 1476 - 1485.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
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]

Home page
 NEJMHome page
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]

Home page
 Nephrol Dial TransplantHome page
G. Walz
Slit or pore? A mutation of the ion channel TRPC6 causes FSGS
Nephrol. Dial. Transplant., September 1, 2005; 20(9): 1777 - 1779.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Lehtonen, J. J. Ryan, K. Kudlicka, N. Iino, H. Zhou, and M. G. Farquhar
Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and {alpha}-actinin are components of the nephrin multiprotein complex
PNAS, July 12, 2005; 102(28): 9814 - 9819.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
M. H. Beall, F. Amidi, D. A. Gayle, S. Wang, R. Beloosesky, and M. G. Ross
Placental and Fetal Membrane Nephrin and Neph1 Gene Expression: Response to Inflammation
Reproductive Sciences, July 1, 2005; 12(5): 298 - 302.
[Abstract] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
B. Bussolati, M. C. Deregibus, V. Fonsato, S. Doublier, T. Spatola, S. Procida, F. Di Carlo, and G. Camussi
Statins Prevent Oxidized LDL-Induced Injury of Glomerular Podocytes by Activating the Phosphatidylinositol 3-Kinase/AKT-Signaling Pathway
J. Am. Soc. Nephrol., July 1, 2005; 16(7): 1936 - 1947.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
G. Wolf, S. Chen, and F. N. Ziyadeh
From the Periphery of the Glomerular Capillary Wall Toward the Center of Disease: Podocyte Injury Comes of Age in Diabetic Nephropathy
Diabetes, June 1, 2005; 54(6): 1626 - 1634.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
K. Tryggvason and J. Wartiovaara
How Does the Kidney Filter Plasma?
Physiology, April 1, 2005; 20(2): 96 - 101.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
R. R. Foster, M. A. Saleem, P. W. Mathieson, D. O. Bates, and S. J. Harper
Vascular endothelial growth factor and nephrin interact and reduce apoptosis in human podocytes
Am J Physiol Renal Physiol, January 1, 2005; 288(1): F48 - F57.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
T. Benzing
Signaling at the Slit Diaphragm
J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1382 - 1391.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the American Society for Investigative Pathology.