ArticleJCI insight2020
Polycystin-1 regulates ARHGAP35-dependent centrosomal RhoA activation and ROCK signaling.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- RhoA through its various effectors mediate mitochondrial fragmentation in polycystic kidney disease.iScience · 2026Article
- An integrin beta-1-anchored bicaudal C1-polycystin-1 module essential for tubular morphogenesis in polycystic kidney disease.iScience · 2026Article
- Abnormal purinergic signaling contributes to development of renal cysts in autosomal dominant polycystic kidney disease.Purinergic signalling · 2026Article
- Lack of ANKMY2 suppresses kidney cystogenesis in embryonic- and adult-onset polycystic kidney disease.PLoS genetics · 2025Article
- miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney disease.Renal failure · 2025Article
- Prostaglandin E2 inhibits adipogenesis through the cilia-dependent activation of ROCK2.Journal of cell science · 2025Article
- Prostaglandin Analogs and Eupatilin as Treatments for Nephronophthisis.Kidney international reports · 2025Article
- Drug and siRNA screens identify ROCK2 as a therapeutic target for ciliopathies.Communications medicine · 2025Article
- Primary cilia prevent activation of the cGAS-STING pathway during mouse decidualization.Communications biology · 2025Article
- Myocardin-Related Transcription Factor Mediates Epithelial Fibrogenesis in Polycystic Kidney Disease.Cells · 2024Article
- The CPLANE protein Fuzzy regulates ciliogenesis by suppressing actin polymerization at the base of the primary cilium via p190A RhoGAP.Development (Cambridge, England) · 2024Article
- Wound healing: insights into autoimmunity, ageing, and cancer ecosystems through inflammation and IL-6 modulation.Frontiers in immunology · 2024Review
- Regulation of the length of neuronal primary cilia and its potential effects on signalling.Trends in cell biology · 2023Review
- Computational study of biomechanical drivers of renal cystogenesis.Biomechanics and modeling in mechanobiology · 2023Article
- Exosomal miR‑152‑5p/ARHGAP6/ROCK axis regulates apoptosis and fibrosis in cardiomyocytes.Experimental and therapeutic medicine · 2023Article
- The Dual Function of RhoGDI2 in Immunity and Cancer.International journal of molecular sciences · 2023Review
- Reducing GEF-H1 Expression Inhibits Renal Cyst Formation, Inflammation, and Fibrosis via RhoA Signaling in Nephronophthisis.International journal of molecular sciences · 2023Article
- Review of the Use of Animal Models of Human Polycystic Kidney Disease for the Evaluation of Experimental Therapeutic Modalities.Journal of clinical medicine · 2023Review
- Primary cilia and actin regulatory pathways in renal ciliopathies.Frontiers in nephrology · 2023Review
- Crosstalk between the mTOR pathway and primary cilia in human diseases.Current topics in developmental biology · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in PKD1 (encoding for polycystin-1 [PC1]) are found in 80%-85% of patients with autosomal dominant polycystic kidney disease (ADPKD). We tested the hypothesis that changes in actin dynamics result from PKD1 mutations through dysregulation of compartmentalized centrosomal RhoA signaling mediated by specific RhoGAP (ARHGAP) proteins resulting in the complex cellular cystic phenotype. Initial studies revealed that the actin cytoskeleton was highly disorganized in cystic cells derived from patients with PKD1 and was associated with an increase in total and centrosomal active RhoA and ROCK signaling. Using cilia length as a phenotypic readout for centrosomal RhoA activity, we identified ARHGAP5, -29, and -35 as essential regulators of ciliation in normal human renal tubular cells. Importantly, a specific decrease in centrosomal ARHGAP35 was observed in PKD1-null cells using a centrosome-targeted proximity ligation assay and by dual immunofluorescence labeling. Finally, the ROCK inhibitor hydroxyfasudil reduced cyst expansion in both human PKD1 3D cyst assays and an inducible Pkd1 mouse model. In summary, we report a potentially novel interaction between PC1 and ARHGAP35 in the regulation of centrosomal RhoA activation and ROCK signaling. Targeting the RhoA/ROCK pathway inhibited cyst formation in vitro and in vivo, indicating its relevance to ADPKD pathogenesis and for developing new therapies to inhibit cyst initiation.
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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.