EPLIN-α and -β Isoforms Modulate Endothelial Cell Dynamics through a Spatiotemporally Differentiated Interaction with Actin

Abstract

Summary: Actin-binding proteins are essential for linear and branched actin filament dynamics that control shape change, cell migration, and cell junction remodeling in vascular endothelium (endothelial cells [ECs]). The epithelial protein lost in neoplasm (EPLIN) is an actin-binding protein, expressed as EPLIN-α and EPLIN-β by alternative promoters; however, the isoform-specific functions are not yet understood. Aortic compared to cava vein ECs and shear stress-exposed cultured ECs express increased EPLIN-β levels that stabilize stress fibers. In contrast, EPLIN-α expression is increased in growing and migrating ECs, is targeted to membrane protrusions, and terminates their growth via interaction with the Arp2/3 complex. The data indicate that EPLIN-α controls protrusion dynamics while EPLIN-β has an actin filament stabilizing role, which is consistent with FRAP analyses demonstrating a lower EPLIN-β turnover rate compared to EPLIN-α. Together, EPLIN isoforms differentially control actin dynamics in ECs, essential in shear stress responses, cell migration, and barrier function. : Dynamics of actin bundles and branched actin filaments in ECs depend on cell activation and actin binding proteins. Taha et al. show that EPLIN-α controls branched actin filament dynamics of classical lamellipodia (cLP) and junction-associated intermittent lamellipodia (JAIL), while EPLIN-β is upregulated in hemodynamically loaded ECs to stabilize actin bundles. Keywords: junction-associated intermittent lamellipodia, JAIL, junction dynamics, Arp2/3 complex, hemodynamics, actin binding proteins, VE-cadherin dynamics, lamellipodia, stress fibers, shear stress