A role for the actin cytoskeleton in the initiation and maintenance of store-mediated calcium entry in human platelets. Evidence for conformational coupling

J Biol Chem. 2000 Mar 17;275(11):7527-33. doi: 10.1074/jbc.275.11.7527.


The nature of the mechanism underlying store-mediated Ca(2+) entry has been investigated in human platelets through a combination of cytoskeletal modifications. Inhibition of actin polymerization by cytochalasin D or latrunculin A had a biphasic time-dependent effect on Ca(2+) entry, showing an initial potentiation followed by inhibition of Ca(2+) entry. Moreover, addition of these agents after induction of store-mediated Ca(2+) entry inhibited the Ca(2+) influx mechanism. Jasplakinolide, which reorganizes actin filaments into a tight cortical layer adjacent to the plasma membrane, prevented activation of store-mediated Ca(2+) entry but did not modify this process after its activation. In addition, jasplakinolide prevented cytochalasin D-induced inhibition of store-mediated Ca(2+) entry. Calyculin A, an inhibitor of protein serine/threonine phosphatases 1 and 2 which activates translocation of existing F-actin to the cell periphery without inducing actin polymerization, also prevented activation of store-mediated Ca(2+) entry. Finally, inhibition of vesicular transport with brefeldin A inhibited activation of store-mediated Ca(2+) entry but did not alter this mechanism once initiated. These data suggest that store-mediated Ca(2+) entry in platelets may be mediated by a reversible trafficking and coupling of the endoplasmic reticulum with the plasma membrane, which shows close parallels to the events mediating secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Biological Transport
  • Blood Platelets / metabolism*
  • Brefeldin A / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Calcium / metabolism*
  • Cell Membrane / metabolism
  • Cytochalasin D / pharmacology
  • Cytoskeleton / metabolism*
  • Depsipeptides*
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Marine Toxins
  • Models, Biological
  • Oxazoles / pharmacology
  • Peptides, Cyclic / pharmacology
  • Thiazoles / pharmacology
  • Thiazolidines


  • Actins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Depsipeptides
  • Marine Toxins
  • Oxazoles
  • Peptides, Cyclic
  • Thiazoles
  • Thiazolidines
  • jasplakinolide
  • Brefeldin A
  • Cytochalasin D
  • calyculin A
  • Inositol 1,4,5-Trisphosphate
  • latrunculin A
  • Calcium