MAGI-2 scaffold protein is critical for kidney barrier function Journal Article
| Authors: | Balbas, M. D.; Burgess, M. R.; Murali, R.; Wongvipat, J.; Skaggs, B. J.; Mundel, P.; Weins, A.; Sawyers, C. L. |
| Article Title: | MAGI-2 scaffold protein is critical for kidney barrier function |
| Abstract: | MAGUK Inverted 2 (MAGI-2) is a PTEN-interacting scaffold protein implicated in cancer on the basis of rare, recurrent genomic translocations and deletions in various tumors. In the renal glomerulus, MAGI-2 is exclusively expressed in podocytes, specialized cells forming part of the glomerular filter, where it interacts with the slit diaphragm protein nephrin. To further explore MAGI-2 function,we generated Magi-2-KO mice through homologous recombination by targeting an exon common to all three alternative splice variants. Magi-2 null mice presented with progressive proteinuria as early as 2 wk postnatally, which coincided with loss of nephrin expression in the glomeruli. Magi-2-null kidneys revealed diffuse podocyte foot process effacement and focal podocyte hypertrophy by 3 wk of age, as well as progressive podocyte loss. By 5.5 wk, coinciding with a near-complete loss of podocytes, Magi-2-nullmice developed diffuse glomerular extracapillary epithelial cell proliferations, and died of renal failure by 3 mo of age. As confirmed by immunohistochemical analysis, the proliferative cell populations in glomerular lesions were exclusively composed of activated parietal epithelial cells (PECs). Our results reveal that MAGI-2 is required for the integrity of the kidney filter and podocyte survival. Moreover, we demonstrate that PECs can be activated to form glomerular lesions resembling a noninflammatory glomerulopathy with extensive extracapillary proliferation, sometimes resembling crescents, following rapid and severe podocyte loss. |
| Keywords: | glomerulosclerosis; magi-2/s-scam |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 111 |
| Issue: | 41 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2014-10-14 |
| Start Page: | 14876 |
| End Page: | 14881 |
| Language: | English |
| DOI: | 10.1073/pnas.1417297111 |
| PROVIDER: | scopus |
| PUBMED: | 25271328 |
| PMCID: | PMC4205655 |
| DOI/URL: | |
| Notes: | Export Date: 3 November 2014 -- Source: Scopus |
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