| First Author | Huber TB | Year | 2009 |
| Journal | J Am Soc Nephrol | Volume | 20 |
| Issue | 4 | Pages | 798-806 |
| PubMed ID | 19279126 | Mgi Jnum | J:164628 |
| Mgi Id | MGI:4834742 | Doi | 10.1681/ASN.2008080871 |
| Citation | Huber TB, et al. (2009) Loss of podocyte aPKClambda/iota causes polarity defects and nephrotic syndrome. J Am Soc Nephrol 20(4):798-806 |
| abstractText | Atypical protein kinase C (aPKC) is a central component of the evolutionarily conserved Par3-Par6-aPKC complex, one of the fundamental regulators of cell polarity. We recently demonstrated that these proteins interact with Neph-nephrin molecules at the slit diaphragm of the glomerular filtration barrier. Here, we report that podocyte-specific deletion of aPKClambda/iota in mice results in severe proteinuria, nephrotic syndrome, and death at 4 to 5 wk after birth. Podocyte foot processes of knockout mice developed structural defects, including mislocalization of the slit diaphragm. In the glomerulus, aPKClambda/iota was primarily expressed in developing glomerular epithelial cells and podocyte foot processes. Interestingly, under physiologic conditions, aPKClambda/iota translocated from the apical surface to the basolateral side of developing podocytes, and this translocation preceded the development of foot processes and formation of slit diaphragms. Supporting a critical role for aPKClambda/iota in the maintenance of slit diaphragms and podocyte foot processes, aPKClambda/iota associated with the Neph-nephrin slit diaphragm complex and localized to the tips of filopodia and leading edges of cultured podocytes. These results suggest that aPKC signaling is fundamental to glomerular maintenance and development. |
