Platelet sarco/endoplasmic reticulum Ca2+ATPase isoform 3b and Rap 1b: Interrelation and regulation in physiopathology

Christine Lacabaratz-Porret, Elisabeth Corvazier, Tünde Kovàcs, Régis Bobe, Raymonde Bredoux, Sophie Launay, Béla Papp, Jocelyne Enouf

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Abstract

Platelet Ca2+ signalling involves intracellular Ca2+ pools, whose content is controlled by sarco/endoplasmic reticulum Ca2+ATPases (SERCAs). Among these, a key role is played by the inositol trisphosphate-sensitive Ca2+ pool, associated with the SERCA 3b isoform. We have investigated the control of this Ca2+ pool through the cAMP-dependent phosphorylation of the GTP-binding protein, Rap (Ras-proximate) 1b. We first looked for this Ca2+ pool target of regulation by studying the expression of the different SERCA and Rap 1 proteins in human platelets and various cell lines, by Western blotting and reverse transcription-PCR. Since co-expression of Rap 1b and SERCA 3b was obtained, we looked for their protein-protein interaction as a function of the cAMP-dependent phosphorylation of Rap 1b. Co-immunoprecipitations of SERCA 3b and Rap 1b proteins were found in the absence of phosphorylation, induced by the catalytic subunit of the cAMP-dependent protein kinase (csPKA). In contrast, upon pre-treatment of platelet membranes with csPKA, the SERCA 3b dissociated from the Rap 1b protein, in agreement with a role of its phosphorylated state in their interaction. Finally, we looked for adaptation of this complex in a platelet pathological model of hypertension. We investigated the expression of both proteins, as well as the cAMP-dependent phosphorylation of Rap 1b and SERCA 3b activity in platelets from control normotensive Wistar-Kyoto rats and from spontaneously hypertensive rats (SHRs). A decrease in SERCA 3b activity was associated with a decrease in Rap 1b endogenous phosphorylation in SHR platelets, consistent with a functional role in the regulation of the SERCA 3b-associated Ca2+ pool.

Original languageEnglish
Pages (from-to)173-181
Number of pages9
JournalBiochemical Journal
Volume332
Issue number1
DOIs
Publication statusPublished - May 15 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Lacabaratz-Porret, C., Corvazier, E., Kovàcs, T., Bobe, R., Bredoux, R., Launay, S., Papp, B., & Enouf, J. (1998). Platelet sarco/endoplasmic reticulum Ca2+ATPase isoform 3b and Rap 1b: Interrelation and regulation in physiopathology. Biochemical Journal, 332(1), 173-181. https://doi.org/10.1042/bj3320173