Leech Colin A, Kopp Richard F, Nelson Heather A, Nandi Jyotirmoy, Roe Michael W
From the Department of Medicine and.
the Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, New York 13210.
J Biol Chem. 2017 Feb 10;292(6):2266-2277. doi: 10.1074/jbc.M116.767681. Epub 2016 Dec 21.
Stromal interaction molecule 1 (STIM1) regulates store-operated Ca entry (SOCE) and other ion channels either as an endoplasmic reticulum Ca-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 of , the gene that encodes STIM1, in insulin-secreting MIN6 β-cells with RNA interference inhibits SOCE and ATP-sensitive K () channel activation. The effects of knockdown were reversed by transduction of MIN6 cells with an adenovirus gene shuttle vector that expressed human Immunoprecipitation studies revealed that STIM1 binds to nucleotide binding fold-1 (NBF1) of the sulfonylurea receptor 1 (SUR1) subunit of the channel. Binding of STIM1 to SUR1 was enhanced by poly-lysine. Our data indicate that SOCE and channel activity are regulated by STIM1. This suggests that STIM1 is a multifunctional signaling effector that participates in the control of membrane excitability and Ca signaling events in β-cells.
基质相互作用分子1（STIM1）作为一种内质网钙传感蛋白或存在于质膜时，可调节储存式钙内流（SOCE）和其他离子通道。然而，STIM1在胰岛素分泌β细胞中的作用尚未明确。我们报道，通过RNA干扰降低胰岛素分泌性MIN6β细胞中编码STIM1的基因的表达，可抑制SOCE和ATP敏感性钾（K）通道激活。用表达人免疫沉淀研究的腺病毒基因穿梭载体转导MIN6细胞可逆转敲低的影响。免疫沉淀研究表明，STIM1与通道磺脲类受体1（SUR1）亚基的核苷酸结合折叠-1（NBF1）结合。聚赖氨酸可增强STIM1与SUR1的结合。我们的数据表明，SOCE和通道活性受STIM1调节。这表明STIM1是一种多功能信号效应器，参与β细胞中膜兴奋性和钙信号事件的控制。
