title: Plasticity in Ca2+ selectivity of Orai1/Orai3 heteromeric channel.
abstract: A general cellular response following depletion of intracellular calcium stores involves activation of store-operated channels (SOCs). While Orai1 forms the native Ca(2+) release-activated Ca(2+) (CRAC) channel in mast and T cells, the molecular architecture of less Ca(2+) selective SOCs is insufficiently defined. Here we present evidence that diminished Ca(2+) selectivity and robust Cs(+) permeation together with a reduced fast inactivation are characteristics of heteromeric Orai1 and Orai3 channels in contrast to their homomeric forms. The first extracellular loop of these Orai isoforms differs by two aspartates replacing glutamates that affect the selectivity. Co-expression of an Orai3 mutant that mimicked the first loop of Orai1 with either Orai1 or Orai3 recovered or decreased Ca(2+) selectivity, respectively. Heteromeric Orai1/3 protein assembly provides a concept for less Ca(2+)-selective SOCs.
authors.affiliation: Institute of Biophysics, University of Linz, A-4040 Linz, Austria. rainer.schindl@jku.at
authors.forename: Rainer
authors.initials: R
authors.lastname: Schindl
authors.forename: Irene
authors.initials: I
authors.lastname: Frischauf
authors.forename: Judith
authors.initials: J
authors.lastname: Bergsmann
authors.forename: Martin
authors.initials: M
authors.lastname: Muik
authors.forename: Isabella
authors.initials: I
authors.lastname: Derler
authors.forename: Barbara
authors.initials: B
authors.lastname: Lackner
authors.forename: Klaus
authors.initials: K
authors.lastname: Groschner
authors.forename: Christoph
authors.initials: C
authors.lastname: Romanin
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002586:Cesium / Q000378:metabolism; D006801:Humans; D000071740:ORAI1 Protein; D055503:Protein Multimerization
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C522867:Orai3 protein, human; D002586:Cesium; D002118:Calcium