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 of STIM1, 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 of STIM1 knockdown were reversed by transduction of MIN6 cells with an adenovirus gene shuttle vector that expressed human STIM1 Immunoprecipitation studies revealed that STIM1 binds to nucleotide binding fold-1 (NBF1) of the sulfonylurea receptor 1 (SUR1) subunit of the KATP channel. Binding of STIM1 to SUR1 was enhanced by poly-lysine. Our data indicate that SOCE and KATP channel 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.
Highlights
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
We demonstrate that STIM1 regulates SOCE in MIN6 cells
We discovered that STIM1 interacts with sulfonylurea receptor 1 (SUR1), a subunit of KATP channels, and functions in KATP channel activation
Summary
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. We report that lowering expression of STIM1, the gene that encodes STIM1, in insulin-secreting MIN6 -cells with RNA interference inhibits SOCE and ATP-sensitive K؉ (KATP) channel activation. Our data indicate that SOCE and KATP channel activity are regulated by STIM1.
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