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
Altmetric
Citation Impact
MSK Authors
  1. Charles L Sawyers
    181 Sawyers
  2. Rajmohan Murali
    168 Murali
  3. Minna Delarae Balbas
    7 Balbas