"NPHS2 is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family."

"NPHS2 is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family"

"We found ten different NPHS2 mutations, comprising nonsense, frameshift and missense mutations, to segregate with the disease, demonstrating a crucial role for podocin in the function of the glomerular filtration barrier."

"In metanephric kidneys, the NPHS2 transcript was initially detected in the lower limb of the late S-shaped body, in the presumptive podocytes but not in future parietal epithelial cells"

"23 Using immunogold labeling and electron microsopy, we showed the podocin distribution at the base of the foot processes and precisely determined its localization on either side of the slit diaphragm, the slit membrane itself being unlabeled"

"Interestingly, both the C- and N-terminal domains of the protein identified by specific antibodies are co-localized at the cytoplasmic face of the plasma membrane, a finding in agreement with the hairpin-like predicted structure of podocin"

"Our results suggest that podocin could serve to anchor directly or indirectly components of the slit diaphragm to the cytoskeleton."

"We report now that NEPH1 belongs to a family of three closely related proteins that interact with the C-terminal domain of podocin"

"All three NEPH proteins share a conserved podocin-binding motif; mutation of a centrally located tyrosine residue dramatically lowers the affinity of NEPH1 for podocin"

"In this study, we confirmed that podocin colocalizes with CAR and ZO-1 at the tight junction between foot processes in nephrotic rats"

"Using primary cultures of rat podocytes, as well as cell lines that co-expressed podocin and CAR, we observed that podocin was recruited to sites of cell-cell contact and that it co-localized with CAR and ZO-1"

"Consistent with this, we found that podociin facilitated the coalescence of preassembled lipid rafts containing CAR and restricted their lateral mobility, the latter likely a result of dynamic actin reorganization and subsequent tethering of CAR-podocin complexes to the cytoskeleton"

"our data suggest that podocin may also serve as a scaffold that links tight junction proteins to the actin cytoskeleton in nephrotic foot processes"

"Interactions between IQGAP1 and podocin or NCK1/2 were detected in podocytes (Figure 3D and 3E)"

"The In situ Proximity Ligation assay confirmed interactions between IQGAP1 and proteins of the slit diaphragm complex, nephrin, MAGI-1, CD2AP, podocin and NCK1/2"

"The hairpin structure positions both the N-terminal region (amino acids 1-100) and the C-terminal region (amino acids 126-383) intracellularly within the cytoplasm."

"Biochemical studies have demonstrated direct binding of cholesterol to podocin through residues in the PHB domain."

"Podocin is present in native slit diaphragms as part of macromolecular assemblies with apparent molecular weights in the range of 1.5-3 megadaltons."

"Podocin lacking the PHB domain (PodocinDeltaPHB) fails to bind cholesterol and does not properly activate TRPC6."

"Mutations in NPHS2 cause autosomal recessive steroid-resistant nephrotic syndrome."

"Podocin is not an enzyme catalyzing a chemical reaction, nor a classical transporter. Instead, convergent evidence supports podocin's primary molecular role as a membrane microdomain organizer/scaffold"

"Primary and mechanistic studies localize podocin to the podocyte slit diaphragm and show it partitions into detergent-resistant membrane (DRM) fractions, consistent with lipid raft association"

"podocin recruits nephrin into lipid raft microdomains at the slit diaphragm, which is necessary for nephrin-dependent signal transduction"

"wild-type podocin augments TRPC6 currents, whereas topology-disrupting mutants fail to do so"

"podocin forms large megadalton complexes mediated by the PHB domain and identify site-specific ubiquitylation (e.g., K301) as affecting stability/unfolding"

"We show that wild-type podocin is targeted to the plasma membrane, and forms homo-oligomers involving the carboxy and amino terminal cytoplasmic domains."

"The association of podocin with specialized lipid raft microdomains of the plasma membrane was a prerequisite for recruitment of nephrin into rafts."

"disease-causing mutations of podocin (R138Q and R138X) failed to recruit nephrin into rafts either because these mutants were retained in the endoplasmic reticulum (R138Q), or because they failed to associate with rafts (R138X) despite their presence in the plasma membrane."

"Our findings demonstrate that the failure of mutant podocin to recruit nephrin into lipid rafts may be essential for the pathogenesis of NPHS2."

"The NPHS2 gene product podocin is a key component of the slit diaphragm cell junction at the kidney filtration barrier and part of a multiprotein-lipid supercomplex."

"podocin and MEC-2 are membrane-associated proteins with a predicted hairpin-like structure and amino and carboxyl termini facing the cytoplasm"

"we show that both mutant proteins, in contrast to the wild-type variants, are N-glycosylated because of the fact that the mutant C termini project extracellularly. Podocin(P118L) and MEC-2(P134S) did not fractionate in detergent-resistant membrane domains."

"the carboxyl terminus of podocin/MEC-2 has to be placed at the inner leaflet of the plasma membrane to mediate cholesterol binding and contribute to ion channel activity, a prerequisite for mechanosensation and the integrity of the kidney filtration barrier."

"mutant podocin failed to activate the ion channel TRPC6, which is part of the multiprotein-lipid supercomplex"

"Podocin and its Caenorhabditis elegans orthologue MEC-2 have emerged as key components of mechanosensitive membrane protein signalling complexes."

"the ubiquitin ligase Ubr4 is a key component of the podocin interactome purified both from cultured podocytes and native glomeruli. It colocalizes with podocin and regulates its stability."

"Ubiquitylomic analysis of mouse glomeruli revealed that podocin is ubiquitylated at two lysine residues. These sites were Ubr4-dependent and were conserved across species."

"ubiquitylation of one site, K301, do not only target podocin/MEC-2 for proteasomal degradation, but may also affect stability and disassembly of the multimeric complex."

"mutations in the NPHS2 gene, which encodes the cholesterol-binding, lipid-raft associated protein podocin"

"Experiments in cell culture could show that this isoform is mostly retained in the endoplasmic reticulum, which is a pathogenic feature known from other disease causing mutations of podocin"

"Mice homozygous for podocinΔexon5 were born heavily albuminuric and did not survive past the first 24 h after birth."

"STED microscopy revealed the complete absence of podocin at the podocytes' slit diaphragm and severe morphological alterations of podocyte foot processes."

"Reduction of podocin levels at the site of the slit diaphragm complex has a detrimental effect on podocyte function and morphology. It is associated with decreased protein abundance of nephrin, the central component of the filtration-slit forming slit diaphragm protein complex."