Two pathways for store-mediated calcium entry differentially dependent on the actin cytoskeleton in human platelets.
A major pathway for stimulated Ca(2+) entry in non-excitable cells is activated following depletion of intracellular Ca(2+) stores. Secretion-like coupling between elements in the plasma membrane (PM) and Ca(2+) stores has been proposed as the most likely mechanism to activate this store-mediated Ca(2+) entry (SMCE) in several cell types. Here we identify two mechanisms for SMCE in human platelets activated by depletion of two independent Ca(2+) pools, which are differentially modulated by the actin cytoskeleton. Ca(2+) entry induced by depletion of a 2,5-di-(tert-butyl)-1,4-hydroquinone (TBHQ)-sensitive pool is increased by disassembly of the actin cytoskeleton and that induced by a TBHQ-insensitive pool is reduced. Stabilization of the actin cytoskeleton prevented Ca(2+) entry by both mechanisms. We propose that the membrane-associated actin network prevents constitutive Ca(2+) entry via both pathways. Reorganization of the actin cytoskeleton permits the activation of Ca(2+) entry via both mechanisms, but only SMCE activated by the TBHQ-insensitive pool requires new actin polymerization, which may support membrane trafficking toward the PM.
Rosado
Juan A
JA
Department of Physiology, University of Extremadura, 10071 Cáceres, Spain. jarosado@unex.es
López
José J
JJ
Harper
Alan G S
AG
Harper
Matthew T
MT
Redondo
Pedro C
PC
Pariente
José A
JA
Sage
Stewart O
SO
Salido
Ginés M
GM
D000199:Actins / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D047630:Depsipeptides; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D018631:ras Proteins / Q000378:metabolism
D000199:Actins; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D019384:Nucleic Acid Synthesis Inhibitors; D010456:Peptides, Cyclic; D013844:Thiazoles; D053778:Thiazolidines; C057531:jasplakinolide; D015638:Cytochalasin D; C018855:2-tert-butylhydroquinone; D018631:ras Proteins; D000252:Calcium-Transporting ATPases; C037067:latrunculin A; D002118:Calcium