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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/F138    most recent 00122.2008v1 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 Web of Science 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 Charba, D. S. Articles by Savin, V. J. PubMed PubMed Citation Articles by Charba, D. S. Articles by Savin, V. J.

Antibodies to protein tyrosine phosphatase receptor type O (PTPro) increase glomerular albumin permeability (P_alb)

¹Rockford Nephrology Associates, Rockford, Illinois; ²Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan; ³University of Kansas Medical Center, Kansas City, Kansas; and ⁴Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 7 March 2008 ; accepted in final form 28 April 2009

Glomerular capillary filtration barrier characteristics are determined in part by the slit-pore junctions of glomerular podocytes. Protein tyrosine phosphatase receptor-O (PTPro) is a transmembrane protein expressed on the apical surface of podocyte foot processes. Tyrosine phosphorylation of podocyte proteins including nephrin may control the filtration barrier. To determine whether PTPro activity is required to maintain glomerular macromolecular permeability, albumin permeability (P_alb) was studied after incubation of glomeruli from normal animals with a series of monoclonal (mAb) and polyclonal antibodies. Reagents included mAbs to rabbit and rat PTPro and polyclonal rabbit immune IgG to rat PTPro. mAb 4C3, specific to the amino acid core of PTPro, decreased its phosphatase activity and increased P_alb of rabbit glomeruli in a time- and concentration-dependent manner. In contrast, mAb P8E7 did not diminish phosphatase activity and did not alter P_alb. Preincubation of 4C3 with PTPro extracellular domain fusion protein blocked glomerular binding and abolished permeability activity. In parallel experiments, P_alb of rat glomeruli was increased by two mAbs (1B4 and 1D1) or by polyclonal anti-rat PTPro. We conclude that PTPro interaction with specific antibodies acutely increases P_alb. The identity of the normal ligand for PTPro and of its substrate, as well as the mechanism by which phosphatase activity of this receptor affects the filtration barrier, remain to be determined.

glomerulus; podocyte; slit-pore junction; filtration barrier

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