title: Expression of a long variant of CRACR2A that belongs to the Rab GTPase protein family in endothelial cells.
abstract: CRACR2A protein is described in T cells as an EF-hand-containing modulator of calcium-release-activated calcium (CRAC) channels. Here we sought relevance to calcium entry of endothelial cells. Unexpectedly, short interfering RNA designed to deplete CRACR2A had no effect on CRAC channels in endothelial cells but reduced the abundance of a protein with about twice the mass of CRACR2A. Reference to gene sequence data indicated the potential for a variant transcript encoding a C-terminal Rab GTPase extension of CRACR2A. Full-length cloning demonstrated expression of the long variant in endothelial cells. It was designated CRACR2A-L. Sequence analysis suggested it to be a previously unrecognised member of the Rab GTPase family. It made a positive contribution to endothelial tube formation. The data suggest that endothelial cells contain a long variant of CRACR2A which is an EF-hand-containing Rab protein that lacks impact on CRAC channels.
authors.affiliation: School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Wilson
authors.affiliation: School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Lynn
authors.initials: L
authors.lastname: McKeown
authors.affiliation: School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Sarka
authors.initials: S
authors.lastname: Tumova
authors.affiliation: School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Medicine, University of Leeds, Leeds LS2 9JT, UK. Electronic address: d.j.beech@leeds.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Beech
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D018919:Neovascularization, Physiologic; D000071740:ORAI1 Protein; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C551025:CRACR2A protein, human; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D034741:RNA, Small Interfering; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D020691:rab GTP-Binding Proteins; D002118:Calcium
keywords: Angiogenesis; Calcium channel; Endothelial cell; G protein; Store-operated calcium entry