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Arpin deficiency increases actomyosin contractility and vascular permeability.

Armando Montoya-Garcia | Idaira M Guerrero-Fonseca | Sandra D Chanez-Paredes | Karina B Hernandez-Almaraz | Iliana I Leon-Vega | Angelica Silva-Olivares | Abigail Betanzos | Monica Mondragon-Castelan | Ricardo Mondragon-Flores | Citlaltepetl Salinas-Lara | Hilda Vargas-Robles | Michael Schnoor
eLife | 2024

Arpin was discovered as an inhibitor of the Arp2/3 complex localized at the lamellipodial tip of fibroblasts, where it regulated migration steering. Recently, we showed that arpin stabilizes the epithelial barrier in an Arp2/3-dependent manner. However, the expression and functions of arpin in endothelial cells (EC) have not yet been described. Arpin mRNA and protein are expressed in EC and downregulated by pro-inflammatory cytokines. Arpin depletion in Human Umbilical Vein Endothelial Cells causes the formation of actomyosin stress fibers leading to increased permeability in an Arp2/3-independent manner. Instead, inhibitors of ROCK1 and ZIPK, kinases involved in the generation of stress fibers, normalize the loss-of-arpin effects on actin filaments and permeability. Arpin-deficient mice are viable but show a characteristic vascular phenotype in the lung including edema, microhemorrhage, and vascular congestion, increased F-actin levels, and vascular permeability. Our data show that, apart from being an Arp2/3 inhibitor, arpin is also a regulator of actomyosin contractility and endothelial barrier integrity.

Pubmed ID: 39298260

Associated grants

  • Agency: Consejo Nacional de Ciencia y Tecnología,
    Id: 284292

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

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