| First Author | Worthmann K | Year | 2013 |
| Journal | Am J Pathol | Volume | 183 |
| Issue | 6 | Pages | 1945-59 |
| PubMed ID | 24096077 | Mgi Jnum | J:202823 |
| Mgi Id | MGI:5522585 | Doi | 10.1016/j.ajpath.2013.08.026 |
| Citation | Worthmann K, et al. (2013) Def-6, a Novel Regulator of Small GTPases in Podocytes, Acts Downstream of Atypical Protein Kinase C (aPKC) lambda/iota. Am J Pathol 183(6):1945-59 |
| abstractText | The atypical protein kinase C (aPKC) isotypes PKClambda/iota and PKCzeta are both expressed in podocytes; however, little is known about differences in their function. Previous studies in mice have demonstrated that podocyte-specific loss of PKClambda/iota leads to a severe glomerular phenotype, whereas mice deficient in PKCzeta develop no renal phenotype. We analyzed various effects caused by PKClambda/iota and PKCzeta deficiency in cultured murine podocytes. In contrast to PKCzeta-deficient podocytes, PKClambda/iota-deficient podocytes exhibited a severe actin cytoskeletal phenotype, reduced cell size, decreased number of focal adhesions, and increased activation of small GTPases. Comparative microarray analysis revealed that the guanine nucleotide exchange factor Def-6 was specifically up-regulated in PKClambda/iota-deficient podocytes. In vivo Def-6 expression is significantly increased in podocytes of PKClambda/iota-deficient mice. Cultured PKClambda/iota-deficient podocytes exhibited an enhanced membrane association of Def-6, indicating enhanced activation. Overexpression of aPKClambda/iota in PKClambda/iota-deficient podocytes could reduce the membrane-associated expression of Def-6 and rescue the actin phenotype. In the present study, PKClambda/iota was identified as an important factor for actin cytoskeletal regulation in podocytes and Def-6 as a specific downstream target of PKClambda/iota that regulates the activity of small GTPases and subsequently the actin cytoskeleton of podocytes. |
