STIM1 regulates acidic Ca2+ store refilling by interaction with SERCA3 in human platelets

Biochem Pharmacol. 2008 Jun 1;75(11):2157-64. doi: 10.1016/j.bcp.2008.03.010. Epub 2008 Mar 22.


Ca(2+) mobilization regulates a wide variety of cellular functions. Platelets possess agonist-releasable Ca(2+) stores in acidic organelles where sarcoendoplasmic reticulum Ca(2+)-ATPase-3 (SERCA) pump is involved in store refilling. Stromal interaction molecule 1 (STIM1), which has been presented as a central regulator of platelet function, is a Ca(2+) sensor of the intracellular Ca(2+) stores. Here we present that STIM1 is required for acidic store refilling. Electrotransjection of cells with anti-STIM1 (Y(231)-K(243)) antibody, directed towards a cytoplasmic sequence of STIM1, significantly reduced acidic store refilling, which was tested by remobilizing Ca(2+) from the acidic stores using 2,5-di-(t-butyl)-1,4-hydroquinone (TBHQ) after a brief refilling period that followed thrombin stimulation. Platelet treatment with thrombin or thapsigargin in combination with ionomycin, to induce extensive Ca(2+) store depletion, resulted in a transient increase in the interaction between STIM1 and SERCA3, reaching a maximum 30 s after stimulation. The coupling between STIM1 and SERCA3 was abolished by electrotransjection with anti-STIM1 antibody. The interaction between STIM1 and SERCA3 induced by thrombin or by treatment with thapsigargin plus ionomycin is reduced in platelets from type 2 diabetic patients, as well as Ca(2+) reuptake into the acidic Ca(2+) stores. These findings provide evidence for a role of STIM1 in acidic store refilling in platelets probably acting as a Ca(2+) sensor and regulating the activity of SERCA3. This action is impaired in platelets from type 2 diabetics, which might lead to the enhanced cytosolic Ca(2+) concentration observed and, therefore, in platelet hyperactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets / cytology
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Diabetes Mellitus, Type 2 / metabolism
  • Fura-2 / pharmacology
  • Gene Expression Regulation
  • Hemostatics / pharmacology
  • Humans
  • Hydroquinones / pharmacology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Rotenone / pharmacology
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism*
  • Stromal Interaction Molecule 1
  • Thrombin / pharmacology
  • Uncoupling Agents / pharmacology


  • Chelating Agents
  • Hemostatics
  • Hydroquinones
  • Membrane Proteins
  • Neoplasm Proteins
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • Uncoupling Agents
  • Rotenone
  • 2-tert-butylhydroquinone
  • Thrombin
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • ATP2A3 protein, human
  • Calcium-Transporting ATPases
  • Calcium
  • Fura-2