title: A STIM2 splice variant negatively regulates store-operated calcium entry.
abstract: Cellular homeostasis relies upon precise regulation of Ca(2+) concentration. Stromal interaction molecule (STIM) proteins regulate store-operated calcium entry (SOCE) by sensing Ca(2+) concentration in the ER and forming oligomers to trigger Ca(2+) entry through plasma membrane-localized Orai1 channels. Here we characterize a STIM2 splice variant, STIM2.1, which retains an additional exon within the region encoding the channel-activating domain. Expression of STIM2.1 is ubiquitous but its abundance relative to the more common STIM2.2 variant is dependent upon cell type and highest in naive T cells. STIM2.1 knockdown increases SOCE in naive CD4(+) T cells, whereas knockdown of STIM2.2 decreases SOCE. Conversely, overexpression of STIM2.1, but not STIM2.2, decreases SOCE, indicating its inhibitory role. STIM2.1 interaction with Orai1 is impaired and prevents Orai1 activation, but STIM2.1 shows increased affinity towards calmodulin. Our results imply STIM2.1 as an additional player tuning Orai1 activation in vivo.
authors.affiliation: Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Building 48, Homburg 66421, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Miederer
authors.affiliation: Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Building 48, Homburg 66421, Germany.
authors.forename: Dalia
authors.initials: D
authors.lastname: Alansary
authors.affiliation: Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Building 48, Homburg 66421, Germany.|Department of Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg 66421, Germany.
authors.forename: Gertrud
authors.initials: G
authors.lastname: Schwär
authors.affiliation: Center for Bioinformatics, Saarland University, Campus E2 1, R. 315, PO Box 151150, Saarbrücken 66041, Germany.
authors.forename: Po-Hsien
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Saarland University, Building 44, Homburg 66421, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Jung
authors.affiliation: Center for Bioinformatics, Saarland University, Campus E2 1, R. 315, PO Box 151150, Saarbrücken 66041, Germany.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Helms
authors.affiliation: Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Building 48, Homburg 66421, Germany.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Niemeyer
mesh_terms: D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D000071740:ORAI1 Protein; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D000071738:Stromal Interaction Molecule 2
chemical_list: D015220:Calcium Channels; D002147:Calmodulin; D015815:Cell Adhesion Molecules; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D020033:Protein Isoforms; C513279:STIM2 protein, human; D000071738:Stromal Interaction Molecule 2; D002118:Calcium