ArticlePLoS genetics2016
A Point Mutation in p190A RhoGAP Affects Ciliogenesis and Leads to Glomerulocystic Kidney Defects.
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.
What it found
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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.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Exome Sequencing in Prenatally Diagnosed Isolated Neural Tube Defects: A Subtype-Specific Analysis.Prenatal diagnosis · 2026Article
- Drug and siRNA screens identify ROCK2 as a therapeutic target for ciliopathies.Communications medicine · 2025Article
- The CPLANE protein Fuzzy regulates ciliogenesis by suppressing actin polymerization at the base of the primary cilium via p190A RhoGAP.Development (Cambridge, England) · 2024Article
- Article
- ARHGAP35 is a novel factor disrupted in human developmental eye phenotypes.European journal of human genetics : EJHG · 2023Article
- Primary cilia and actin regulatory pathways in renal ciliopathies.Frontiers in nephrology · 2023Review
- The p190 RhoGAPs, ARHGAP35, and ARHGAP5 are implicated in GnRH neuronal development: Evidence from patients with idiopathic hypogonadotropic hypogonadism, zebrafish, and in vitro GAP activity assay.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- Roles of the actin cytoskeleton in ciliogenesis.Journal of cell science · 2022Review
- Myocardin-related transcription factor and serum response factor regulate cilium turnover by both transcriptional and local mechanisms.iScience · 2021Article
- Kinase-anchoring proteins in ciliary signal transduction.The Biochemical journal · 2021Review
- Ciliary extracellular vesicles are distinct from the cytosolic extracellular vesicles.Journal of extracellular vesicles · 2021Article
- Polycystin-1 regulates ARHGAP35-dependent centrosomal RhoA activation and ROCK signaling.JCI insight · 2020Article
- p190A RhoGAP induces CDH1 expression and cooperates with E-cadherin to activate LATS kinases and suppress tumor cell growth.Oncogene · 2020Article
- Primary Cilia, Ciliogenesis and the Actin Cytoskeleton: A Little Less Resorption, A Little More Actin Please.Frontiers in cell and developmental biology · 2020Review
- Involvement of ARHGEF10, GEF for RhoA, in Rab6/Rab8-mediating membrane traffic.Small GTPases · 2019Review
- p190RhoGAPs, theCells · 2019Review
- Regulation of Rho GTPase activity at the leading edge of migrating cells by p190RhoGAP.Small GTPases · 2019Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
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.
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Registered trials
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.