Stromal Interaction Molecule 1 (STIM1) Regulates ATP-sensitive Potassium ( K ATP ) and Store-operated Ca 2+ Channels in MIN6 β-Cells

• Published in: The Journal of biological chemistry Vol. 292; no. 6; p. 2266
• Main Authors: Leech, Colin A, Kopp, Richard F, Nelson, Heather A, Nandi, Jyotirmoy, Roe, Michael W
• Format: Journal Article
• Language: English
• Published: United States 10-02-2017
• Subjects: Animals; Calcium Channels - physiology; Calcium Signaling; Cell Line; Gene Knockdown Techniques; Humans; Ion Transport; Islets of Langerhans - metabolism; KATP Channels - physiology; Mice; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Stromal Interaction Molecule 1 - genetics; Stromal Interaction Molecule 1 - physiology; KATP channels; Ca2+ signaling; STIM1; electrophysiology; SUR1; cell signaling; store-operated ion channels; endoplasmic reticulum (ER); beta cell (B-cell); calcium imaging
• ISSN: 1083-351X

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.