Cadherin superfamily in intercellular junctions of podocytes in the kidney

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During a search for cadherin-related molecules expressed in rat glomeruli by PT-PCR with degenerate primers, we have isolated cDNA encoding a rat homologue of human FAT.FAT, a new member of the cadherin superfamily, resembles the Drosophila tumor suppressor fat. It is a large transmembrane protein with 34 tandem cadherin-like repeats, five EGF-like repeats, and a laminin A-G domain, indicating its potential role in cell-cell adhesion and cell proliferation. To localize FAT and to speculate its role in the kidney, we examined its expression in the rat neonatal and adult kidney in the physiological and pathological conditons by using ribonuclease protection assay (RPA), in situ hybridization(ISH) and immunostaining.Comparison of the deduced amino acid sequences showed more than 85% identical residues in rat and human FAT, especially, 100% identical in C-terminus of FAT of the both species. Affinity-purified antibody against FAT C-terminus was prepared. RPA revealed significant signals in RNA from glomeruli of the normal rat kidney. By ISH, FAT expression was observed in podocytes. Immunostaining for FAT was coincident with that of 5.1.6, which is antibody specific for slit diaphragm. In PAN nephrosis, conspicuous increase in FAT expression in glomeruli was shown by RPA, ISH, and immunostaining. In the neonatal kidney, FAT was observed in podocytes throughout the development from S-shaped body to mature glomeruli.The above findings suggest that FAT is one of basic constitutents of intercellular junctions of podocytes.