title: CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry.
abstract: Store-operated Ca2+ entry is mediated by Ca2+ release-activated Ca2+ (CRAC) channels following Ca2+ release from intracellular stores. We performed a genome-wide RNA interference (RNAi) screen in Drosophila cells to identify proteins that inhibit store-operated Ca2+ influx. A secondary patch-clamp screen identified CRACM1 and CRACM2 (CRAC modulators 1 and 2) as modulators of Drosophila CRAC currents. We characterized the human ortholog of CRACM1, a plasma membrane-resident protein encoded by gene FLJ14466. Although overexpression of CRACM1 did not affect CRAC currents, RNAi-mediated knockdown disrupted its activation. CRACM1 could be the CRAC channel itself, a subunit of it, or a component of the CRAC signaling machinery.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. mvig@bidmc.harvard.edu
authors.forename: M
authors.initials: M
authors.lastname: Vig
authors.forename: C
authors.initials: C
authors.lastname: Peinelt
authors.forename: A
authors.initials: A
authors.lastname: Beck
authors.forename: D L
authors.initials: DL
authors.lastname: Koomoa
authors.forename: D
authors.initials: D
authors.lastname: Rabah
authors.forename: M
authors.initials: M
authors.lastname: Koblan-Huberson
authors.forename: S
authors.initials: S
authors.lastname: Kraft
authors.forename: H
authors.initials: H
authors.lastname: Turner
authors.forename: A
authors.initials: A
authors.lastname: Fleig
authors.forename: R
authors.initials: R
authors.lastname: Penner
authors.forename: J-P
authors.initials: JP
authors.lastname: Kinet
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D000071740:ORAI1 Protein; D018408:Patch-Clamp Techniques; D034622:RNA Interference; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015220:Calcium Channels; D029721:Drosophila Proteins; D008565:Membrane Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D034741:RNA, Small Interfering; C510832:dpr3 protein, Drosophila; C510747:olf186-F protein, Drosophila; D002118:Calcium