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 cell–cell 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.
Highlights
The formation of new blood vessels through angiogenesis involves endothelial cell (EC) adhesion, migration and proliferation and is critical for embryo development and tissue regeneration (Potente et al, 2011)
Depletion of Coronin 1B (Coro1B) in ECs leads to defects in actin cytoskeleton organization, reduced number of Junction-associated intermitted lamellipodia (JAIL), altered cell–cell junction morphology and impaired endothelial network assembly
It has been shown that JAIL, actin-driven and actin related protein 2/3 (Arp2/3) complex-controlled plasma membrane protrusions that develop at cell–cell junction sites with decreased or lost VEcad, regulate the local dynamics and patterning of VEcad, thereby controlling junctional integrity and monolayer formation in vitro and sprouting angiogenesis in vivo (Fraccaroli et al, 2015; Cao et al, 2017)
Summary
The formation of new blood vessels through angiogenesis involves endothelial cell (EC) adhesion, migration and proliferation and is critical for embryo development and tissue regeneration (Potente et al, 2011). JAIL driving VEcad dynamics within the cell–cell junction is critical for monolayer integrity, cell migration and angiogenesis (Abu et al, 2014; Fraccaroli et al, 2015; Cao et al, 2017). Actin-binding proteins regulate actin cytoskeleton dynamics thereby controlling the remodeling of endothelial cell–cell junctions, cell migration and vessel integrity (Pollard et al, 2000; Edwards et al, 2014). Type I coronins, such as coronin 1B (Coro1B), localize to the leading edge of migrating cells where they regulate actin dynamics in the lamellipodia via both Arp2/3 complex and cofilin-mediated pathways (Mishima and Nishida, 1999; Chan et al, 2011). In the current study we identify Coro1B as a new regulator of JAIL formation, cell–cell junction and the assembly of endothelial network in vitro
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