Bves: ten years after

Abstract

Bves was discovered in 1999 by two independent laboratories using screens to identify novel genes that were highly expressed in the developing heart (Reese et al., 1999; Andree et al., 2000). As an evolutionarily conserved transmembrane protein, Bves is postulated to play a role in cell adhesion and cell motility. In studies of Bves protein disruption, there have been multiple phenotypes, but few molecular mechanisms have been advanced to explain the underlying cause of these phenotypes. As the molecular function of Bves protein begins to be uncovered, it is now time to review the literature to examine the significance of this work and future directions of study. This review summarizes the literature on this unique protein and explores new and exciting data that support emerging themes on its molecular function.

Fig. 1

The Popdc Family. Bves is only 25% conserved with either Popdc2 or Popdc3, suggesting it is the outlier of this gene family. The function of Bves is only now being uncovered, whereas the function of Popdc2 and Popdc3 are completely unknown.

Fig. 2

Bves Protein. Bves is a transmembrane protein that exists in the plasma membrane as a multimer. There is a short, extracellular N-terminus with two N-glycosylation sites and an intracellular, self-associating C-terminus. Located within the C-terminus is the Popeye domain, named for its high conservation across species. To date, no function has been specifically linked to this motif.

Fig. 3

Bves Expression. Bves is expressed in cells that associate or couple: Heart (A), Skeletal Muscle (B), Brain (C) and Epithelia (D).

Fig. 4

Bves Regulation of GEFT. In order to induce downstream effectors, GEFT must be activated (A); the mechanism by which this occurs is not specifically known. Bves interaction with GEFT may regulate the activation state of GEFT. Three mechanisms of modulation are outlined: 1) Bves may sequester GEFT, resulting in decreased activation of effector proteins (B). 2) Bves may directly activate GEFT through its interaction (C). 3) Bves may indirectly regulate the activation state of GEFT by localizing it to the membrane (D).