ATP depletion induces translocation of STIM1 to puncta and formation of STIM1-ORAI1 clusters: translocation and re-translocation of STIM1 does not require ATP

Pflugers Arch. 2008 Nov;457(2):505-17. doi: 10.1007/s00424-008-0529-y. Epub 2008 Jun 10.

Abstract

Depletion of the endoplasmic reticulum (ER) calcium store triggers translocation of stromal interacting molecule one (STIM1) to the sub-plasmalemmal region and formation of puncta-structures in which STIM1 interacts and activates calcium channels. ATP depletion induced the formation of STIM1 puncta in PANC1, RAMA37, and HeLa cells. The sequence of events triggered by inhibition of ATP production included a rapid decline of ATP, depletion of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) and a slow calcium leak from the ER followed by formation of STIM1 puncta. STIM1 puncta induced by ATP depletion were co-localized with clusters of ORAI1 channels. STIM1-ORAI1 clusters that developed as a result of ATP depletion were very poor mediators of Ca(2+) influx. Re-translocation of STIM1 from puncta back to the ER was observed during total ATP depletion. We can therefore conclude that STIM1 translocation and re-translocation as well as formation of STIM1-ORAI1 clusters occur in an ATP-independent fashion and under conditions of PI(4,5)P(2) depletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / deficiency*
  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Signaling* / drug effects
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Calcium-Transporting ATPases / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / metabolism*
  • Enzyme Inhibitors / pharmacology
  • HeLa Cells
  • Humans
  • Kinetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microscopy, Confocal
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • ORAI1 Protein
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Protein Binding
  • Protein Transport
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Stromal Interaction Molecule 1
  • Thapsigargin / pharmacology
  • Transfection

Substances

  • Calcium Channels
  • Enzyme Inhibitors
  • Membrane Proteins
  • Neoplasm Proteins
  • ORAI1 Protein
  • ORAI1 protein, human
  • Phosphatidylinositol 4,5-Diphosphate
  • Recombinant Fusion Proteins
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • Thapsigargin
  • Adenosine Triphosphate
  • Calcium-Transporting ATPases