title: Regulation of Ca2+ release-activated Ca2+ channels by INAD and Ca2+ influx factor.
abstract: The coupling mechanism between depletion of Ca(2+) stores in the endoplasmic reticulum and plasma membrane store-operated ion channels is fundamental to Ca(2+) signaling in many cell types and has yet to be completely elucidated. Using Ca(2+) release-activated Ca(2+) (CRAC) channels in RBL-2H3 cells as a model system, we have shown that CRAC channels are maintained in the closed state by an inhibitory factor rather than being opened by the inositol 1,4,5-trisphosphate receptor. This inhibitory role can be fulfilled by the Drosophila protein INAD (inactivation-no after potential D). The action of INAD requires Ca(2+) and can be reversed by a diffusible Ca(2+) influx factor. Thus the coupling between the depletion of Ca(2+) stores and the activation of CRAC channels may involve a mammalian homologue of INAD and a low-molecular-weight, diffusible store-depletion signal.
authors.affiliation: Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
authors.forename: Zhengchang
authors.initials: Z
authors.lastname: Su
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Barker
authors.forename: Peter
authors.initials: P
authors.lastname: Csutora
authors.forename: Theresa
authors.initials: T
authors.lastname: Chang
authors.forename: Richard L
authors.initials: RL
authors.lastname: Shoemaker
authors.forename: Richard B
authors.initials: RB
authors.lastname: Marchase
authors.forename: J Edwin
authors.initials: JE
authors.lastname: Blalock
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D029721:Drosophila Proteins; D005057:Eukaryotic Cells / Q000187:drug effects / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D001896:Boron Compounds; D015220:Calcium Channels; D029721:Drosophila Proteins; D005136:Eye Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C091568:inaD protein, Drosophila; D006493:Heparin; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium