Filtrin is a novel member of nephrin-like proteins

NPHS1 encodes nephrin. the core protein of the interpodocyte slit diaphragm of the kidney glomerulus. NPHSI is the causative gene for congenital nephrotic syndrome of the Finnish type (CNF) with massive, treatment resistant proteinuria. We report here the establishment of a novel nephrin-like gene, NLG1 encoding filtrin, a protein with substantial homology to human nephrin. Filtrin is a type I transmembrane protein consisting of 708 amino acids. Together with the recently cloned NEPH1, NLGI establishes a new nephrin-like subgroup of genes belonging to the immunoglobulin superfamily of cell adhesion molecules. The RNA dot blot experiment revealed that the NLGI mRNA expression is widely distributed but most prominently observed in the pancreas and lymph nodes. The expression of NLGI mRNA in kidney glomeruli was verified with RT-PCR. Further immunoblotting studies with antifiltrin antibody showed a specific band at 107 kDa in the human and rat glomeruli. In immunofluorescence microscopy specific staining of glomeruli but also proximal and distal parts of the nephron was seen in human kidney cortex. Due to its structural similarity and sequence homology as well as partially consistent expression pattern with nephrin we propose that filtrin belongs to a functionally important complex of proteins of the glomerular filtration barrier. (C) 2002 Elsevier Science (USA). All rights reserved.