Coronin 1B Controls Endothelial Actin Dynamics at Cell–Cell Junctions and Is Required for Endothelial Network Assembly

Abstract

Development and homeostasis of blood vessels critically depend on the regulation of endothelial cell-cell junctions. VE-cadherin (VEcad)-based cell-cell junctions are connected to the actin cytoskeleton and regulated by actin-binding proteins. Coronin 1B (Coro1B) is an actin binding protein that controls actin networks at classical lamellipodia. The role of Coro1B in endothelial cells (ECs) is not fully understood and investigated in this study. Here, we demonstrate that Coro1B is a novel component and regulator of cell-cell junctions in ECs. Immunofluorescence studies show that Coro1B colocalizes with VEcad at cell-cell junctions in monolayers of ECs. Live-cell imaging reveals that Coro1B is recruited to, and operated at actin-driven membrane protrusions at cellcell junctions. Coro1B is recruited to cell-cell junctions via a mechanism that requires the relaxation of the actomyosin cytoskeleton. By analyzing the Coro1B interactome, we identify integrin-linked kinase (ILK) as new Coro1B-associated protein. Coro1B colocalizes with α-parvin, an interactor of ILK, at the leading edge of lamellipodia protrusions. Functional experiments reveal that depletion of Coro1B causes defects in the actin cytoskeleton and cell-cell junctions. Finally, in matrigel tube network assays, depletion of Coro1B results in reduced network complexity, tube number and tube length. Together, our findings point toward a critical role for Coro1B in the dynamic remodeling of endothelial cell-cell junctions and the assembly of endothelial networks.

Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells

“…Silenced or kinase dead CORO1B has been shown to reduce migration in a multitude of different cancer and non-cancer cells [126][127][128][129].…”

“…CORO1B regulates various actin‐dependent cellular processes via Arp2/3 complex interactions promoting cell protrusion, migration and scission [126]. Silenced or kinase dead CORO1B has been shown to reduce migration in a multitude of different cancer and non‐cancer cells [126–129]. In addition, type I cornonins have been associated with poor prognosis and metastasis in GC [130, 131].…”

Actin cytoskeleton in angiogenesis

“…Actin binding proteins like coronin 1B ( Werner et al, 2020 ), α-Parvin ( Fraccaroli et al, 2015 ), and EPLIN α and β ( Taha et al, 2019 ) are critical regulators of JAIL formation ( Seebach et al, 2020 ). In summary, JAILs and JBL are under the control of mechanical cues like shear stress or stretch.…”

Biomechanical and biochemical assessment of YB-1 expression in A375 melanoma cell line: Exploratory study

“…Immunolabelling of F-actin in YB-1 knock-out cell line demonstrated a spectrum of mesenchymal phenotypes, including lamellipodia, or filopodia. We found strong upregulation of coronins, including Coronin 1B (Coro1B) which is actin binding protein that controls actin networks at classical lamellipodia ( Werner et al, 2020 ). Vinculin and zyxin are adaptor proteins involved in forming more stable focal adhesions ( Panková et al, 2010 ), while tissue transglutaminase (TGM2) promotes adhesion, spreading of cells, and enhances focal adhesions which are crucial to mesenchymal migrating cells ( Fok et al, 2006 ).…”