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Plasma membrane Ca2+ -ATPase (PMCA) translocates to filopodia during platelet activation

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: https://doi.org/10.1160/TH03-07-0425
Issue: 2004: 91/2 (Feb) pp. 210-415
Pages: 325-333

Plasma membrane Ca2+ -ATPase (PMCA) translocates to filopodia during platelet activation

William L. Dean (1) , Sidney W. Whiteheart (2)
(1) Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky, USA (2) Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, USA

Summary

The plasma membrane Ca2+ -ATPase (PMCA) plays an essential role in maintaining low cytosolic Ca2+ in platelets. Recently we demonstrated that PMCA is recruited to the cytoskeleton by interacting with PDZ domains. In the present study we determined the subcellular localization of PMCA using immu-nofluorescence microscopy. In resting platelets PMCA was dis-tributed over the entire plasma membrane. Upon activation with thrombin, PMCA was found in filopodia adjacent to the actin cytoskeleton. PMCA translocation to filopodia was pre-vented by a peptide containing the last 10 residues of PMCA4b, the predominate isoform of PMCA in platelets, which contains a known PDZ domain-binding motif and was previously shown to block association of PMCA with the cytoskeleton. Incorporation of the PMCA C-terminal peptide did not affect the rate or extent of platelet aggregation, but significantly enhanced the rate of clot retraction. These results show that PMCA association with the cytoskeleton during platelet activa-tion results in translocation of this Ca 2+ -pump to filopodia and that this association may affect later stages of platelet activa-tion. The consequence of PMCA translocation to filopodia is likely a reduction in the local concentration of free Ca 2+ in these structures resulting in regulation of the rate of clot retraction.