[Molecular dynamics of proteins found exclusively in glomerular epithelial cells]

The visceral glomerular epithelial cells or podocytes of the renal glomerulus are uniquely characterized by a large cell body and numerous foot processes. These foot processes are kept wide open to facilitate passage of glomerular filtrate and are held together tenuous slit diaphragms that bridge the filtration slits. By contrast, nephrosis results in the apical displacement of the glomerular filtration slit membrane by newly formed intercellular occluding-type junctions. It is still unknown what kind of proteins are involved in the morphological changes of podocytes in nephrotic conditions. Our data show that one isoform of ZO-1 found exclusively in the tight junction(TJ) is expressed in the highly specialized slit diaphragm. In nephrotic rats induced by puromycin aminonucleoside(PAN) treatment or perfusion with polycations such as protamine sulfate(PS), the slit diaphragms are displaced by occluding-type junctions. In these cases, ZO-1 was concentrated along both the newly formed occluding-type junctions and the remaining slit diaphragms. Also, perfusion of glomeruli with polycations induces tyrosine phosphorylation of some proteins including ZO-1 within 15 min. What kind of molecules contribute to such a signal transduction? A possible candidate is podocalyxin, which is the major sialoglycoprotein of the rat glomerular epithelial cell. We cloned rat podocalyxin gene and analyzed its molecular nature. Furthermore, we have made a number of monoclonal antibodies against rat podocytes. Monoclonal antibody P-31 we made recognizes a novel intermediate filament-associated protein(p250) in rat podocytes. Our data suggest that p250 would play a important role in the organization of the intermediate filament network in both normal and diseased conditions.