Evidence map›Paper›PMID 26859289›Full record

ArticlePLoS genetics2016

A Point Mutation in p190A RhoGAP Affects Ciliogenesis and Leads to Glomerulocystic Kidney Defects.

Katherine Stewart, Yaned Gaitan, Maxwell E R Shafer, Lamine Aoudjit, Di Hu, Richa Sharma, Mathieu Tremblay, Hidetaka Ishii, Michael Marcotte, Daniela Stanga and 7 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 17% 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

17 citing papers in PubMed, 28 citations in OpenAlex.

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  16. p190RhoGAPs, theCells · 2019
    Review
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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

17 authors at 2 institutions in 1 country.

Katherine StewartGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Yaned GaitanGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Maxwell E R ShaferGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Lamine AoudjitDepartment of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
Di HuGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Richa SharmaGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Mathieu TremblayGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Hidetaka IshiiDepartment of Anatomy and Cell Biology, McGill University, and Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Michael MarcotteGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Daniela StangaGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
You Chi TangGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Sami Kamel BoualiaGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Alana H T NguyenGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Tomoko TakanoDepartment of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
Nathalie Lamarche-VaneDepartment of Anatomy and Cell Biology, McGill University, and Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Silvia VidalDepartment of Human Genetics and Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Maxime BouchardGoodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
McGill University Health Centre · CAMcGill University · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Rho family GTPases act as molecular switches regulating actin cytoskeleton dynamics. Attenuation of their signaling capacity is provided by GTPase-activating proteins (GAPs), including p190A, that promote the intrinsic GTPase activity of Rho proteins. In the current study we have performed a small-scale ENU mutagenesis screen and identified a novel loss of function allele of the p190A gene Arhgap35, which introduces a Leu1396 to Gln substitution in the GAP domain. This results in decreased GAP activity for the prototypical Rho-family members, RhoA and Rac1, likely due to disrupted ordering of the Rho binding surface. Consequently, Arhgap35-deficient animals exhibit hypoplastic and glomerulocystic kidneys. Investigation into the cystic phenotype shows that p190A is required for appropriate primary cilium formation in renal nephrons. P190A specifically localizes to the base of the cilia to permit axoneme elongation, which requires a functional GAP domain. Pharmacological manipulations further reveal that inhibition of either Rho kinase (ROCK) or F-actin polymerization is able to rescue the ciliogenesis defects observed upon loss of p190A activity. We propose a model in which p190A acts as a modulator of Rho GTPases in a localized area around the cilia to permit the dynamic actin rearrangement required for cilia elongation. Together, our results establish an unexpected link between Rho GTPase regulation, ciliogenesis and glomerulocystic kidney disease.

Indexed as

OrganogenesisActinsAllelesAmino Acid SequenceAmino Acid SubstitutionAnimalsCiliaCytoskeletonEmbryo, MammalianEthylnitrosoureaFemaleFibroblastsGTPase-Activating ProteinsKidney Diseases, CysticKidney GlomerulusKidney TubulesActinsArhgap35 protein, mouseEthylnitrosoureaGTPase-Activating ProteinsRepressor Proteins

Identifiers

PMID26859289
PMCPMC4747337
OpenAlexW2262055873

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.