Verge: a novel vascular early response gene.
Vascular endothelium forms a continuous, semipermeable barrier that regulates the transvascular movement of hormones, macromolecules, and other solutes. Here, we describe a novel immediate early gene that is expressed selectively in vascular endothelial cells, verge (vascular early response gene). Verge protein includes an N-terminal region of approximately 70 amino acids with modest homology (approximately 30% identity) to Apolipoprotein L but is otherwise unique. Verge mRNA and protein are induced selectively in the endothelium of adult vasculature by electrical or chemical seizures. Verge expression appears to be responsive to local tissue conditions, because it is induced in the hemisphere ipsilateral to transient focal cerebral ischemia. In contrast to the transient expression in adult, Verge mRNA and protein are constitutively expressed at high levels in the endothelium of developing tissues (particularly heart) in association with angiogenesis. Verge mRNA is induced in cultured endothelial cells by defined growth factors and hypoxia. Verge protein is dramatically increased by cysteine proteinase inhibitors, suggesting rapid turnover, and is localized to focal regions near the periphery of the cells. Endothelial cell lines that stably express Verge form monolayers that show enhanced permeability in response to activation of protein kinase C by phorbol esters. This response is accompanied by reorganization of the actin cytoskeleton and the formation of paracellular gaps. These studies suggest that Verge functions as a dynamic regulator of endothelial cell signaling and vascular function.
Regard
Jean B
JB
Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Scheek
Sigrid
S
Borbiev
Talaibek
T
Lanahan
Anthony A
AA
Schneider
Armin
A
Demetriades
Anna-Maria
AM
Hiemisch
Holger
H
Barnes
Carol A
CA
Verin
Alexander D
AD
Worley
Paul F
PF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002545:Brain Ischemia / Q000378:metabolism; D015687:Cell Hypoxia; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020536:Enzyme Activators / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D017781:Genes, Immediate-Early / Q000235:genetics*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D009928:Organ Specificity; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection
C488170:Apold1 protein, rat; D020536:Enzyme Activators; D006133:Growth Substances; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D011493:Protein Kinase C