Bves: prototype of a new class of cell adhesion molecules expressed during coronary artery development

Abstract

Bves is a protein expressed in cells of the developing coronary vascular system, specifically in the proepicardium, migrating epithelial epicardium, delaminated vasculogenic mesenchyme and vascular smooth muscle cells. Here, we show that Bves protein undergoes a dynamic subcellular redistribution during coronary vessel development. Bves is a membrane protein with three predicted transmembrane helices, an extracellular C terminus and an intracellular N terminus, and is confined to the lateral membrane compartment of epithelial cells. When epicardial cells are dissociated into single cells in vitro, Bves accumulates in a perinuclear region until cells make contact, at which time Bves is trafficked to the cell membrane. Bves accumulates at points of cell/cell contact, such as filopodia and cell borders, before the appearance of E-cadherin, suggesting an early role in cell adhesion. While Bves shares no homology with any known adhesion molecule, transfection of Bves into L-cells readily confers adhesive behavior to these cells. Finally, Bves antibodies inhibit epithelial migration of vasculogenic cells from the proepicardium. This study provides direct evidence that Bves is a novel cell adhesion molecule and suggests a role for Bves in coronary vasculogenesis.