EPLIN-α and -β Isoforms Modulate Endothelial Cell Dynamics Through a Spatio-Temporally Differentiated Interaction with Actin

Abstract

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 (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 EC express increased EPLIN-β levels that stabilizes stress fibers. In contrast, EPLIN-α expression is increased in growing and migrating ECs, appear at the forefront of membrane protrusion 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, cell migration and barrier function.