Molecular structure and function of the slit diaphragm: expression of nephrin in proteinuric states and in developing glomeruli

Nephrin is identified as a product of the gene mutated in a patient with congenital nephrotic syndrome of the Finnish type. To analyse the function of nephrin and the relationship of nephrin and the target antigen of nephritogenic anti‐rat slit diaphragm monoclonal antibody (mAb) 5‐1‐6, the rat homo...

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Published in:Nephrology, dialysis, transplantation dialysis, transplantation, 2002-01, Vol.17 (suppl-9), p.20-22
Main Authors: Kawachi, Hiroshi, Koike, Hiroko, Shimizu, Fujio
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Capillary Permeability
Embryo, Mammalian - physiology
Embryonic and Fetal Development
Fundamental and applied biological sciences. Psychology
Glomerulonephritis
Kidney Glomerulus - blood supply
Kidney Glomerulus - embryology
Medical sciences
Membrane Proteins
monoclonal antibody 5‐1‐6
nephrin
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Nephrotic Syndrome - metabolism
Proteins - metabolism
proteinuria
Rats
slit diaphragm
Vertebrates: urinary system
ZO‐1
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Summary:Nephrin is identified as a product of the gene mutated in a patient with congenital nephrotic syndrome of the Finnish type. To analyse the function of nephrin and the relationship of nephrin and the target antigen of nephritogenic anti‐rat slit diaphragm monoclonal antibody (mAb) 5‐1‐6, the rat homologue of nephrin was cloned. The deduced amino acid sequence of rat nephrin shows 82.2% homology to human nephrin. Signal sequences of rat nephrin are 36 amino acids, whereas those of human nephrin are reported to be 22 amino acids. The localization of rat nephrin always coincided with that of mAb 5‐1‐6 antigen. The specific anti‐nephrin antibody recognized the mAb 5‐1‐6‐antigen complex. mAb 5‐1‐6 reacted with COS cells transfected with rat nephrin cDNA. These results demonstrate that nephritogenic mAb 5‐1‐6 identifies the extracellular domain of rat nephrin, thereby documenting that nephrin is a functional protein of the slit diaphragm. The staining pattern of nephrin shifted from a linear‐like pattern to a discontinuous coarse granular pattern not only in mAb 5‐1‐6‐induced nephropathy, but also in puromycin aminonucleoside nephropathy, adriamycin nephropathy and passive Heymann nephropathy. Rat nephrin is detected first on the basal and lateral side below the junctional complex at the S‐shaped body stage. With the interdigitation of foot processes, nephrin becomes concentrated in the slit pore, and finally restricted in the site of the slit diaphragm bridging two adjacent foot processes.
ISSN:0931-0509
1460-2385
1460-2385
DOI:10.1093/ndt/17.suppl_9.20