Def-6, a novel regulator of small GTPases in podocytes, acts downstream of atypical protein kinase C (aPKC) λ/ι
Worthmann K, Leitges M, Teng B, Sestu M, Tossidou I, Samson T, Haller H, Huber TB, Schiffer M (2013)
Publication Type: Journal article
Publication year: 2013
Journal
Book Volume: 183
Pages Range: 1945-1959
Journal Issue: 6
DOI: 10.1016/j.ajpath.2013.08.026
Abstract
The atypical protein kinase C (aPKC) isotypes PKCλ/ι and PKCζ 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 PKCλ/ι leads to a severe glomerular phenotype, whereas mice deficient in PKCζ develop no renal phenotype. We analyzed various effects caused by PKCλ/ι and PKCζ deficiency in cultured murine podocytes. In contrast to PKCζ-deficient podocytes, PKCλ/ι-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 PKCλ/ι-deficient podocytes. In vivo Def-6 expression is significantly increased in podocytes of PKCλ/ι-deficient mice. Cultured PKCλ/ι-deficient podocytes exhibited an enhanced membrane association of Def-6, indicating enhanced activation. Overexpression of aPKCλ/ι in PKCλ/ι-deficient podocytes could reduce the membrane-associated expression of Def-6 and rescue the actin phenotype. In the present study, PKCλ/ι was identified as an important factor for actin cytoskeletal regulation in podocytes and Def-6 as a specific downstream target of PKCλ/ι that regulates the activity of small GTPases and subsequently the actin cytoskeleton of podocytes. © 2013 American Society for Investigative Pathology.
Authors with CRIS profile
Involved external institutions
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
University of North Carolina at Chapel Hill
United States (USA) (US)
University of Oslo
Norway (NO)
Universität Leipzig
Germany (DE)
Universitätsklinikum Freiburg
Germany (DE)
Germany (DE)
University of North Carolina at Chapel Hill
United States (USA) (US)
University of Oslo
Norway (NO)
Universität Leipzig
Germany (DE)
Universitätsklinikum Freiburg
Germany (DE)
How to cite
APA:
Worthmann, K., Leitges, M., Teng, B., Sestu, M., Tossidou, I., Samson, T.,... Schiffer, M. (2013). Def-6, a novel regulator of small GTPases in podocytes, acts downstream of atypical protein kinase C (aPKC) λ/ι. American Journal of Pathology, 183(6), 1945-1959. https://doi.org/10.1016/j.ajpath.2013.08.026
MLA:
Worthmann, Kirstin, et al. "Def-6, a novel regulator of small GTPases in podocytes, acts downstream of atypical protein kinase C (aPKC) λ/ι." American Journal of Pathology 183.6 (2013): 1945-1959.
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