title: Stromal Interaction Molecule 1 (STIM1) Regulates ATP-sensitive Potassium (KATP) and Store-operated Ca2+Channels in MIN6 β-Cells.
abstract: Stromal interaction molecule 1 (STIM1) regulates store-operated Ca2+entry (SOCE) and other ion channels either as an endoplasmic reticulum Ca2+-sensing protein or when present in the plasma membrane. However, the role of STIM1 in insulin-secreting β-cells is unresolved. We report that lowering expression ofSTIM1, the gene that encodes STIM1, in insulin-secreting MIN6 β-cells with RNA interference inhibits SOCE and ATP-sensitive K+(KATP) channel activation. The effects ofSTIM1knockdown were reversed by transduction of MIN6 cells with an adenovirus gene shuttle vector that expressed humanSTIM1Immunoprecipitation studies revealed that STIM1 binds to nucleotide binding fold-1 (NBF1) of the sulfonylurea receptor 1 (SUR1) subunit of theKATPchannel. Binding of STIM1 to SUR1 was enhanced by poly-lysine. Our data indicate that SOCE andKATPchannel activity are regulated by STIM1. This suggests that STIM1 is a multifunctional signaling effector that participates in the control of membrane excitability and Ca2+signaling events in β-cells.
authors.affiliation: From the Department of Medicine and.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Leech
authors.affiliation: From the Department of Medicine and.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kopp
authors.affiliation: the Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, New York 13210.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Nelson
authors.affiliation: From the Department of Medicine and.
authors.forename: Jyotirmoy
authors.initials: J
authors.lastname: Nandi
authors.affiliation: From the Department of Medicine and roem@upstate.edu.|the Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, New York 13210.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Roe
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling; D002460:Cell Line; D055785:Gene Knockdown Techniques; D006801:Humans; D017136:Ion Transport; D007515:Islets of Langerhans / Q000378:metabolism*; D054086:KATP Channels / Q000502:physiology*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D000071737:Stromal Interaction Molecule 1 / Q000235:genetics / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D054086:KATP Channels; D009363:Neoplasm Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1
keywords: Ca2+ signaling; KATP channels; STIM1; SUR1; beta cell (B-cell); calcium imaging; cell signaling; electrophysiology; endoplasmic reticulum (ER); store-operated ion channels