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OBJECTIVE: We aimed to characterize the expression and function of a novel transcript that bioinformatics analysis predicted to be endothelial specific, called endothelial-specific molecule-2 (ECSM2). METHODS AND RESULTS: A full-length cDNA was isolated and predicted ECSM2 to be a putative 205-amino acid transmembrane protein that bears no homology to any known protein. Quantitative polymerase chain reaction analysis in vitro and in situ hybridization analysis in vivo confirmed ECSM2 expression to be exclusively endothelial, and localization to the plasma membrane was shown. Knockdown of ECSM2 expression in human umbilical vein endothelial cells using siRNA resulted in both reduced chemotaxis and impaired tube formation on matrigel, a solubilized basement membrane, both processes involved in angiogenesis. A yeast 2 hybrid analysis using the ECSM2 intracellular domain identified filamin A as an interacting protein. This interaction was confirmed by precipitation of filamin-A from endothelial cell lysates by a GST-tagged intracellular domain of ECSM2. CONCLUSIONS: This study is the first to characterize a novel cell surface protein ECSM2 that regulates endothelial chemotaxis and tube formation, and interacts with filamin A. These studies implicate a role for ECSM2 in angiogenesis via modulation of the actin cytoskeleton.

Original publication

DOI

10.1161/atvbaha.108.162511

Type

Journal article

Journal

Arteriosclerosis, thrombosis, and vascular biology

Publication Date

09/2008

Volume

28

Pages

1640 - 1646

Addresses

Angiogenesis Laboratory, Cancer Research UK, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford.

Keywords

Cells, Cultured, Cell Membrane, Endothelial Cells, Humans, Microfilament Proteins, Contractile Proteins, Membrane Proteins, Recombinant Fusion Proteins, RNA, Small Interfering, In Situ Hybridization, Cloning, Molecular, Two-Hybrid System Techniques, Transfection, Polymerase Chain Reaction, Chemotaxis, RNA Interference, Amino Acid Sequence, Neovascularization, Physiologic, Molecular Sequence Data