Store-operated cyclic AMP signalling mediated by STIM1

Nat Cell Biol. 2009 Apr;11(4):433-42. doi: 10.1038/ncb1850. Epub 2009 Mar 15.

Abstract

Depletion of Ca(2+) from the endoplasmic reticulum (ER) results in activation of plasma membrane Ca(2+) entry channels. This 'store-operated' process requires translocation of a transmembrane ER Ca(2+) sensor protein, stromal interaction molecule 1 (STIM1), to sites closely apposed to Ca(2+) channels at the cell surface. However, it is not known whether a reduction in Ca(2+) stores is coupled to other signalling pathways by this mechanism. We found that lowering the concentration of free Ca(2+) in the ER, independently of the cytosolic Ca(2+) concentration, also led to recruitment of adenylyl cyclases. This resulted in enhanced cAMP accumulation and PKA activation, measured using FRET-based cAMP indicators. Translocation of STIM1 was required for efficient coupling of ER Ca(2+) depletion to adenylyl cyclase activity. We propose the existence of a pathway (store-operated cAMP signalling or SOcAMPS) in which the content of internal Ca(2+) stores is directly connected to cAMP signalling through a process that involves STIM1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Calcium / metabolism
  • Calcium Signaling* / drug effects
  • Cell Line
  • Chelating Agents / pharmacology
  • Cyclic AMP / biosynthesis
  • Cyclic AMP / metabolism*
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism
  • Enzyme Activation / drug effects
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / metabolism*
  • Phosphoric Diester Hydrolases / metabolism
  • Protein Transport / drug effects
  • Stromal Interaction Molecule 1

Substances

  • Chelating Agents
  • Membrane Proteins
  • Neoplasm Proteins
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • Cyclic AMP
  • Phosphoric Diester Hydrolases
  • Adenylyl Cyclases
  • Calcium