Characterization of Bves expression during mouse development using newly generated immunoreagents

Abstract

Bves (blood vessel/epicardial substance) is a transmembrane protein postulated to play a role in cell-cell interaction/adhesion. It was independently isolated by two groups as a gene product highly enriched in the developing heart. Disagreement exists about its expression during development. Most notably, the expression of Bves in non-muscle cells is disputed. Determining the expression profile of Bves is a critical initial step preceding the characterization of protein function in development and in the adult. We have generated new monoclonal antibodies against mouse Bves and used these immunoreagents to elucidate Bves expression in development. As expected, we detect Bves in myocytes of the developing heart throughout development. In addition, skeletal and smooth muscle cells including those of the coronary system express Bves. Finally, specific, but not all, epithelial derivatives of the three germ layers are stained positively with these monoclonal antibodies. Protein expression in cultured epithelial and muscle cell lines corroborate our in vivo findings. Taken together, these results demonstrate the expression of Bves in a wide range of epithelial and muscle cells during mouse embryogenesis and indicate a broad function for this protein in development, and show that these newly generated reagents will be invaluable in further investigation of Bves.

Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity

“…In the first model, Bves would control the nucleotide binding ability of GEFT. As shown previously, Bves preferentially localizes to the plasma membrane (6,10,14). GEFT contains a pleckstrin homology domain, which has been demonstrated to localize Dbl family GEFs to the membrane (50,51).…”

“…As both Bves and GEFT are highly expressed in muscle (2,6,20,26), we next examined their localization in mouse hindlimb muscle, the heart, and intestinal smooth muscle. As shown in Fig.…”

“…Bves was discovered by our laboratory in 1999, and is widely expressed throughout development and adulthood in many different species. All three developing germ layers (1), cardiac muscle (2-6), skeletal muscle (2,6,7), neural tissues (1, 2), epicardium (1,(8)(9)(10)(11)(12), epithelial components of the eye (13), and smooth muscle (1,6) have been demonstrated to express bves. Although expression of the Bves protein is now resolved, few definitive indications of molecular function exist.…”

Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice

“…The membrane localization of Popdc1 and Popdc2 in cardiac myocytes (22), the high expression level in cardiac pacemaking tissue, and the heart rate-dependent phenotypes in null mutants suggest an electrical function of Popdc proteins. The I f current is an essential part of the network of ion channels that act together to generate the pacemaker potential.…”

Popeye domain-containing 1 is down-regulated in failing human hearts

“…POPDC1, also known as blood vessel epicardial substance (BVES), has been identified in eukaryotes from insects to man, whereas POPDC2 and 3 have only been found in higher vertebrates (3,(6)(7)(8). POPDC1 has been proposed to play a role in cell adhesion and cell signaling as it has been found to be localized at sites of intercellular contacts, bound to the signaling modifier guanine nucleotide exchange factor T, and has been shown to be involved in Rho signaling and receptor cycling (8)(9)(10)(11)(12)(13). Experiments using Popdc1-null mice have indicated an impaired ability for skeletal muscle regeneration (14) and an increased sensitivity of the heart to ischemia-reperfusion injury (Alcalay et al, unpublished data).…”