Evidence map›Paper›PMID 24096077›Full record

ArticleThe American journal of pathology2013

Def-6, a novel regulator of small GTPases in podocytes, acts downstream of atypical protein kinase C (aPKC) λ/ι.

Kirstin Worthmann, Michael Leitges, Beina Teng, Marcello Sestu, Irini Tossidou, Thomas Samson, Hermann Haller, Tobias B Huber, Mario Schiffer

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 3 countries.

Kirstin WorthmannDivision of Nephrology, Department of Medicine, Hannover Medical School, Hannover, Germany.
Michael LeitgesBiotechnology Centre of Oslo, University of Oslo, Oslo, Norway.
Beina TengDivision of Nephrology, Department of Medicine, Hannover Medical School, Hannover, Germany.
Marcello SestuFaculty of Medicine, Interdisciplinary Centre for Clinical Research (IZKF) Leipzig, University of Leipzig, Leipzig, Germany.
Irini TossidouDivision of Nephrology, Department of Medicine, Hannover Medical School, Hannover, Germany.
Thomas SamsonDepartment of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
Hermann HallerDivision of Nephrology, Department of Medicine, Hannover Medical School, Hannover, Germany.
Tobias B HuberRenal Division, University Hospital Freiburg, Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany.
Mario SchifferDivision of Nephrology, Department of Medicine, Hannover Medical School, Hannover, Germany. Electronic address: schiffer.mario@mh-hannover.de.
Medizinische Hochschule Hannover · DELeipzig University · DEUniversity of Freiburg · DEUniversity of North Carolina at Chapel Hill · USUniversity of Oslo · NO

Funding

STRUCTURE/FUNCTION OF FOCAL ADHESIONSR01GM029860 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BURRIDGE, KEITH · 1985 to 2018
$6.7M
NIGMS NIH HHS GM029860NIGMS NIH HHS R01 GM029860
6 · The paper itself

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.

Indexed as

Actin CytoskeletonAnimalsCell MembraneCells, CulturedDNA-Binding ProteinsGene Expression RegulationGTP PhosphohydrolasesGuanine Nucleotide Exchange FactorsIsoenzymesMiceMice, KnockoutNuclear ProteinsPodocytesProtein Kinase CProtein Kinase C-epsilonProtein Kinase C-lambdaDef6 protein, mouseDNA-Binding ProteinsGTP PhosphohydrolasesGuanine Nucleotide Exchange FactorsIsoenzymesNuclear ProteinsProtein Kinase CProtein Kinase C-epsilonProtein Kinase C-lambda

Identifiers

PMID24096077
PMCPMC5707189
OpenAlexW2031389630

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.