ArticleHuman molecular genetics2014
Polycystin-1 regulates actin cytoskeleton organization and directional cell migration through a novel PC1-Pacsin 2-N-Wasp complex.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- PACSIN2-mediated synaptic injury contributes to behavioral disorders caused by chronic stress.Acta pharmacologica Sinica · 2026Article
- Deep learning-supported image quantification of epithelial cell shapes and its application to polycystic kidney disease.PLoS computational biology · 2026Article
- EZH2 inhibition or genetic ablation suppresses cyst growth in autosomal dominant polycystic kidney disease.Journal of translational medicine · 2024Article
- Article
- Glucose absorption drives cystogenesis in a human organoid-on-chip model of polycystic kidney disease.Nature communications · 2022Article
- Organoid-on-a-chip model of human ARPKD reveals mechanosensing pathomechanisms for drug discovery.Science advances · 2022Article
- Fission yeast paxillin contains two Cdc15 binding motifs for robust recruitment to the cytokinetic ring.Molecular biology of the cell · 2022Article
- PACSIN proteins in vivo: Roles in development and physiology.Acta physiologica (Oxford, England) · 2022Review
- PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders.Cellular and molecular life sciences : CMLS · 2022Article
- The GPCR properties of polycystin-1- A new paradigm.Frontiers in molecular biosciences · 2022Review
- Cytopenia in autosomal dominant polycystic kidney disease (ADPKD): merely an association or a disease-related feature with prognostic implications?Pediatric nephrology (Berlin, Germany) · 2021Review
- The state of F-BAR domains as membrane-bound oligomeric platforms.Trends in cell biology · 2021Review
- Caveolin1 Tyrosine-14 Phosphorylation: Role in Cellular Responsiveness to Mechanical Cues.The Journal of membrane biology · 2020Review
- Polycystin-1 Regulates Actomyosin Contraction and the Cellular Response to Extracellular Stiffness.Scientific reports · 2019Article
- Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population.BMC medical genomics · 2019Article
- The association between autosomal dominant polycystic kidney disease and cancer.International urology and nephrology · 2019Review
- BAR domain proteins-a linkage between cellular membranes, signaling pathways, and the actin cytoskeleton.Biophysical reviews · 2018Review
- Profiling of miRNAs and target genes related to cystogenesis in ADPKD mouse models.Scientific reports · 2017Article
- PACSIN2 accelerates nephrin trafficking and is up-regulated in diabetic kidney disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Deciphering the BAR code of membrane modulators.Cellular and molecular life sciences : CMLS · 2017Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
How epithelial cells form a tubule with defined length and lumen diameter remains a fundamental question in cell and developmental biology. Loss of control of tubule lumen size in multiple organs including the kidney, liver and pancreas features polycystic kidney disease (PKD). To gain insights into autosomal dominant polycystic kidney disease, we performed yeast two-hybrid screens using the C-terminus of polycystin-1 (PC1) as bait. Here, we report that PC1 interacts with Pacsin 2, a cytoplasmic phosphoprotein that has been implicated in cytoskeletal organization, vesicle trafficking and more recently in cell intercalation during gastrulation. PC1 binds to a 107-residue fragment containing the α3 helix of the F-BAR domain of Pacsin 2 via a coiled-coil domain in its C-tail. PC1 and Pacsin 2 co-localize on the lamellipodia of migrating kidney epithelial cells. PC1 and Pacsin 2-deficient kidney epithelial cells migrate at a slower speed with reduced directional persistency. We further demonstrate that PC1, Pacsin 2 and N-Wasp are in the same protein complex, and both PC1 and Pacsin 2 are required for N-Wasp/Arp2/3-dependent actin remodeling. We propose that PC1 modulates actin cytoskeleton rearrangements and directional cell migration through the Pacsin 2/N-Wasp/Arp2/3 complex, which consequently contributes to the establishment and maintenance of the sophisticated tubular architecture. Disruption of this complex contributes to cyst formation in PKD.
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