Expression of Podocalyxin Inhibits Cell–Cell Adhesion and Modifies Junctional Properties in Madin-Darby Canine Kidney Cells

Takeda, Takeshi; Go, William Y.; Orlando, Robert A.; Farquhar, Marilyn G.

doi:10.1091/mbc.11.9.3219

Cited by 184 publications

(200 citation statements)

References 46 publications

Supporting

Mentioning

182

Contrasting

Unclassified

Order By: Relevance

“…61 Previously we showed that expression of podocalyxin, another podocyte protein that associates with actin and maintains the filtration slits open in glomeruli, inhibits cell-cell adhesion and decreases TER in MDCK cells. 62 Our finding that nephrin associates with ZO-1 in MDCK-nephrin cells may explain the effects of nephrin expression on the properties of tight junctions because ZO-1 localizes to the cytoplasmic surface of tight junctions and serves as the major scaffolding protein for tight junction strands. 12,13 In conclusion, we show here that nephrin is a component of a large protein complex composed of cell adhesion receptors and cytosolic scaffolding proteins that connect the complex to the actin cytoskeleton and to signaling networks.…”

Section: Discussionmentioning

confidence: 77%

Nephrin Forms a Complex with Adherens Junction Proteins and CASK in Podocytes and in Madin-Darby Canine Kidney Cells Expressing Nephrin

Lehtonen

Kudlicka

Holthöfer

et al. 2004

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 77%

Nephrin Forms a Complex with Adherens Junction Proteins and CASK in Podocytes and in Madin-Darby Canine Kidney Cells Expressing Nephrin

Lehtonen

Kudlicka

Holthöfer

et al. 2004

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Mice lacking podocalyxin (podx1 Ϫ/Ϫ ) die soon after birth with defective kidney development and anuria (18) consistent with podocalyxin acting as an antiadhesin on the podocyte surface to ensure filtration slits remain patent. The importance of glycosylation in podocalyxin function is highlighted by the removal of sialic acid, which has been shown to affect cell adhesion and junctional permeability (19). Because plt1͞plt1 mice are able to produce urine, hypoglycosylated podocalyxin appears sufficient for at least partial renal function.…”

Section: Discussionmentioning

confidence: 99%

Thrombocytopenia and kidney disease in mice with a mutation in the C1galt1 gene

Alexander

Viney

Zhang

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

An N-ethyl-N-nitrosourea mutagenesis screen in mice was performed to isolate regulators of circulating platelet number. We report here recessive thrombocytopenia and kidney disease in plt1 mice, which is the result of a severe but partial loss-of-function mutation in the gene encoding glycoprotein-N-acetylgalactosamine-3-␤-galactosyltransferase (C1GalT1), an enzyme essential for the synthesis of extended mucin-type O-glycans. Platelet half-life and basic hemostatic parameters were unaffected in plt1͞plt1 mice, and the thrombocytopenia and kidney disease were not attenuated on a lymphocyte-deficient rag1-null background. gpIb␣ and podocalyxin were found to be major underglycosylated proteins in plt1͞plt1 platelets and the kidney, respectively, implying that these are key targets for C1GalT1, appropriate glycosylation of which is essential for platelet production and kidney function. Compromised C1GalT1 activity has been associated with immune-mediated diseases in humans, most notably Tn syndrome and IgA nephropathy. The disease in plt1͞plt1 mice suggests that, in addition to immune-mediated effects, intrinsic C1Gal-T1 deficiency in megakaryocytes and the kidney may contribute to pathology. core 1 galactosyltransferase ͉ N-ethyl-N-nitrosourea mutagenesis ͉ nephropathy ͉ platelet

show abstract

“…For example, in the podocytes of the kidney glomerulus, PODXL repels cells from one another (37), whereas in vascular endothelial cells, it plays a pro-adhesive role as a ligand for Lselectin (38). These differences in function are likely due to differences in the glycosylation state of the large extracellular domain of the protein.…”

Section: Discussionmentioning

confidence: 99%

“…Expression of PODXL in normal tissue has been reported as limited to glomerular podocytes, vascular endothelial cells, platelets, hematopoietic stem cells, and mesothelial cells (38,42,43) as well as to prostate tissue. 4 The anti-adhesive function of PODXL in the kidney glomerulus is essential for maintaining the slit diaphragms between podocyte foot processes through which the urine is filtered (37). PODXL Ϫ/Ϫ mice die soon after birth due to anuric renal failure (44).…”

Section: Discussionmentioning

confidence: 99%

The Wilms Tumor Suppressor-1 Target Gene Podocalyxin Is Transcriptionally Repressed by p53

Stanhope-Baker¹,

Kessler²,

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Wilms tumor is a pediatric kidney cancer that affects 1 in 10,000 children. The Wilms tumor suppressor-1 (WT1) 1 gene was identified as a tumor suppressor gene based upon the presence of WT1 mutations in a subset (ϳ10 -15%) of Wilms tumor samples (reviewed in Ref. 1). However, the majority of Wilms tumor cases cannot be explained by genetic alteration of the WT1 locus. There may be disruption of biological pathways either upstream or downstream of WT1, or there may be pathways independent of WT1 leading to this type of neoplasm. Several lines of evidence suggest that p53 also plays an important role in the development and/or progression of Wilms tumors. The p53 and WT1 tumor suppressor genes encode transcription factors that have been shown to interact physically and to modulate each other's function in some experimental situations (2). p53 can alter the transcription regulatory activity of WT1. In addition, WT1 stabilizes the p53 protein, alters its activity as a transcription factor, and prevents p53-induced apoptosis (2, 3). Physical and functional interaction has also been observed between the p53 family members p73 and p63 and WT1 (4). Further evidence for biologically relevant interaction between WT1 and p53 includes the fact that the majority of Wilms tumors develop in the presence of wild-type p53 (5). This is in contrast to adult onset human tumors, in which p53 mutations are frequently observed (ϳ50%). The small subset of Wilms tumors that do harbor p53 mutations develop into much more aggressive anaplastic tumors (between 3 and 7% of the total) that are characterized by unfavorable histology, increased metastasis, chemoresistance, and poor prognosis (6 -9). Moreover, Li-Fraumeni patients carrying germ-line p53 mutations are predisposed to development of Wilms tumors (10), and Wilms tumors are one of a small number of cancers that are specifically associated with such mutations (11). To better understand the involvement of both p53 and WT1 in pathways leading to Wilms tumorigenesis, we have used cDNA microarrays to profile gene expression changes dependent upon the activity of these two factors.To accomplish this, we developed strategies to alter the function of WT1 and p53 in a Wilms tumor cell line, WiT49. This cell line is characteristic of anaplastic Wilms tumors in that it expresses wild-type WT1 and mutant p53. We have previously shown that WT1 activity can be effectively abrogated in WiT49 cells by expression of a naturally occurring dominant-negative mutant version of the protein (DDS5) (12). To restore wild-type p53 function in WiT49 cells, we made use of the small molecule compound CP-31398 developed by Pfizer. CP-31398 was originally shown to stabilize the p53 protein with mutation at codon 173, 175, 249, or 273 in the wild-type conformation and to allow its transcriptional and tumor suppressor functions (13). More recently, it has been shown that CP-31398 can stabilize the wild-type p53 protein as well (14 -16). We found here that CP-31398 restores activity to the codon 248 mutant p53 prese...

show abstract

Expression of Podocalyxin Inhibits Cell–Cell Adhesion and Modifies Junctional Properties in Madin-Darby Canine Kidney Cells

Cited by 184 publications

References 46 publications

Nephrin Forms a Complex with Adherens Junction Proteins and CASK in Podocytes and in Madin-Darby Canine Kidney Cells Expressing Nephrin

Nephrin Forms a Complex with Adherens Junction Proteins and CASK in Podocytes and in Madin-Darby Canine Kidney Cells Expressing Nephrin

Thrombocytopenia and kidney disease in mice with a mutation in the C1galt1 gene

The Wilms Tumor Suppressor-1 Target Gene Podocalyxin Is Transcriptionally Repressed by p53

Contact Info

Product

Resources

About