title: Antibodies to protein tyrosine phosphatase receptor type O (PTPro) increase glomerular albumin permeability (P(alb)).
abstract: 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.
authors.affiliation: Rockford Nephrology Associates, Rockford, Illinois, USA.
authors.forename: Deane S
authors.initials: DS
authors.lastname: Charba
authors.forename: Roger C
authors.initials: RC
authors.lastname: Wiggins
authors.forename: Meera
authors.initials: M
authors.lastname: Goyal
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Wharram
authors.forename: Jocelyn E
authors.initials: JE
authors.lastname: Wiggins
authors.forename: Ellen T
authors.initials: ET
authors.lastname: McCarthy
authors.forename: Ram
authors.initials: R
authors.lastname: Sharma
authors.forename: Mukut
authors.initials: M
authors.lastname: Sharma
authors.forename: Virginia J
authors.initials: VJ
authors.lastname: Savin
mesh_terms: D000418:Albumins / Q000378:metabolism*; D000419:Albuminuria / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000418:Albumins; D000911:Antibodies, Monoclonal; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3