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Science 8 October 1999:
Vol. 286. no. 5438, pp. 312 - 315
DOI: 10.1126/science.286.5438.312
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Reports

Congenital Nephrotic Syndrome in Mice Lacking CD2-Associated Protein

Neng-Yao Shih, 1* Jun Li, 1* Vladimir Karpitskii, 1 Ancho Nguyen, 1 Michael L. Dustin, 1 Osami Kanagawa, 1 Jeffrey H. Miner, 2 Andrey S. Shaw 1dagger

CD2-associated protein (CD2AP) is an 80-kilodalton protein that is critical for stabilizing contacts between T cells and antigen-presenting cells. In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells. Knockout mice exhibited defects in epithelial cell foot processes, accompanied by mesangial cell hyperplasia and extracellular matrix deposition. Supporting a role for CD2AP in the specialized cell junction known as the slit diaphragm, CD2AP associated with nephrin, the primary component of the slit diaphragm.

1 Center for Immunology and Department of Pathology,
2 Department of Medicine, Renal Division, Washington University, Saint Louis, MO 63110, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: shaw{at}immunology.wustl.edu

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Nephrin and CD2AP Associate with Phosphoinositide 3-OH Kinase and Stimulate AKT-Dependent Signaling.
T. B. Huber, B. Hartleben, J. Kim, M. Schmidts, B. Schermer, A. Keil, L. Egger, R. L. Lecha, C. Borner, H. Pavenstadt, et al. (2003)
Mol. Cell. Biol. 23, 4917-4928
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A Novel Protein, Densin, Expressed by Glomerular Podocytes.
H. Ahola, E. Heikkila, E. Astrom, M. Inagaki, I. Izawa, H. Pavenstadt, D. Kerjaschki, and H. Holthofer (2003)
J. Am. Soc. Nephrol. 14, 1731-1737
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In Vivo Expression of Putative LMX1B Targets in Nail-Patella Syndrome Kidneys.
L. Heidet, E. M. H. F. Bongers, M. Sich, S.-Y. Zhang, C. Loirat, A. Meyrier, M. Broyer, G. Landthaler, B. Faller, Y. Sado, et al. (2003)
Am. J. Pathol. 163, 145-155
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Linkage Analysis of Candidate Loci for End-Stage Renal Disease due to Diabetic Nephropathy.
S. K. Iyengar, K. A. Fox, M. Schachere, F. Manzoor, M. E. Slaughter, A. M. Covic, S. M. Orloff, P. S. Hayden, J. M. Olson, J. R. Schelling, et al. (2003)
J. Am. Soc. Nephrol. 14, S195-201
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Linking the T Cell Surface Protein CD2 to the Actin-capping Protein CAPZ via CMS and CIN85.
N. J. Hutchings, N. Clarkson, R. Chalkley, A. N. Barclay, and M. H. Brown (2003)
J. Biol. Chem. 278, 22396-22403
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Cell Biological and Biochemical Characterization of Drebrin Complexes in Mesangial Cells and Podocytes of Renal Glomeruli.
W. K. Peitsch, I. Hofmann, N. Endlich, S. Pratzel, C. Kuhn, H. Spring, H.-J. Grone, W. Kriz, and W. W. Franke (2003)
J. Am. Soc. Nephrol. 14, 1452-1463
   Abstract »    Full Text »    PDF »
Podocyte Differentiation and Hereditary Proteinuria/Nephrotic Syndromes.
M.-C. Gubler (2003)
J. Am. Soc. Nephrol. 14, S22-26
   Abstract »    Full Text »    PDF »
Fyn Binds to and Phosphorylates the Kidney Slit Diaphragm Component Nephrin.
R. Verma, B. Wharram, I. Kovari, R. Kunkel, D. Nihalani, K. K. Wary, R. C. Wiggins, P. Killen, and L. B. Holzman (2003)
J. Biol. Chem. 278, 20716-20723
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CD2-Associated Protein Haploinsufficiency Is Linked to Glomerular Disease Susceptibility.
J. M. Kim, H. Wu, G. Green, C. A. Winkler, J. B. Kopp, J. H. Miner, E. R. Unanue, and A. S. Shaw (2003)
Science 300, 1298-1300
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Nephrin and Neph1 Co-localize at the Podocyte Foot Process Intercellular Junction and Form cis Hetero-oligomers.
G.-M. Barletta, I. A. Kovari, R. K. Verma, D. Kerjaschki, and L. B. Holzman (2003)
J. Biol. Chem. 278, 19266-19271
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Angiogenic Protein Cyr61 is Expressed by Podocytes in Anti-Thy-1 Glomerulonephritis.
K. Sawai, K. Mori, M. Mukoyama, A. Sugawara, T. Suganami, M. Koshikawa, K. Yahata, H. Makino, T. Nagae, Y. Fujinaga, et al. (2003)
J. Am. Soc. Nephrol. 14, 1154-1163
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Broadening the Spectrum of Diseases Related to Podocin Mutations.
G. Caridi, R. Bertelli, M. Di Duca, M. Dagnino, F. Emma, A. Onetti Muda, F. Scolari, N. Miglietti, G. Mazzucco, L. Murer, et al. (2003)
J. Am. Soc. Nephrol. 14, 1278-1286
   Abstract »    Full Text »    PDF »
Neutralization of Circulating Vascular Endothelial Growth Factor (VEGF) by Anti-VEGF Antibodies and Soluble VEGF Receptor 1 (sFlt-1) Induces Proteinuria.
H. Sugimoto, Y. Hamano, D. Charytan, D. Cosgrove, M. Kieran, A. Sudhakar, and R. Kalluri (2003)
J. Biol. Chem. 278, 12605-12608
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The Carboxyl Terminus of Neph Family Members Binds to the PDZ Domain Protein Zonula Occludens-1.
T. B. Huber, M. Schmidts, P. Gerke, B. Schermer, A. Zahn, B. Hartleben, L. Sellin, G. Walz, and T. Benzing (2003)
J. Biol. Chem. 278, 13417-13421
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CD2BP3, CIN85 and the structurally related adaptor protein CMS bind to the same CD2 cytoplasmic segment, but elicit divergent functional activities.
E. V. Tibaldi and E. L. Reinherz (2003)
Int. Immunol. 15, 313-329
   Abstract »    Full Text »    PDF »
Podocyte Differentiation and Glomerulogenesis.
J. A. Kreidberg (2003)
J. Am. Soc. Nephrol. 14, 806-814
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Alternatively Used Promoters and Distinct Elements Direct Tissue-Specific Expression of Nephrin.
O. Beltcheva, S. Kontusaari, S. Fetissov, H. Putaala, P. Kilpelainen, T. Hokfelt, and K. Tryggvason (2003)
J. Am. Soc. Nephrol. 14, 352-358
   Abstract »    Full Text »    PDF »


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