Three novel sarco/endoplasmic reticulum Ca 2+-ATPase (SERCA) 3 isoforms: Expression, regulation, and function of the members of the SERCA3 family

Virginie Martin, Raymonde Bredoux, Elisabeth Corvazier, Roosje Van Gorp, Tünde Kovàcs, Pascal Gélébart, Jocelyne Enouf

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Abstract

Sarco/endoplasmic reticulum Ca 2+-ATPases (SERCAs) pump Ca 2+ into the endoplasmic reticulum. Recently, three human SERCA3 (h3a-c) proteins and a previously unknown rat SERCA3 (r3b/c) mRNA have been described. Here, we (i) document two novel human SERCA3 splice variants h3d and h3e, (ii) provide data for the expression and mechanisms regulating the expression of all known SERCA3 variants (r3a, r3b/c, and h3a-e), and (iii) show functional characteristics of the SERCA3 isoforms. h3d and h3e are issued from the insertion of an additional penultimate exon 22 resulting in different carboxyl termini for these variants. Distinct distribution patterns of the SERCA3 gene products were observed in a series of cell lines of hematopoietic, epithelial, embryonic origin, and several cancerous types, as well as in panels of rat and human tissues. Hypertension and protein kinase C, calcineurin, or retinoic acid receptor signaling pathways were found to differently control rat and human splice variant expression, respectively. Stable overexpression of each variant was performed in human embryonic kidney 293 cells, and the SERCA3 isoforms were fully characterized. All SERCA3 isoforms were found to pump Ca 2+ with similar affinities. However, they modulated the cytosolic Ca 2+ concentration ([Ca 2+] c) and the endoplasmic reticulum Ca 2+ content ([Ca 2+] er) in different manners. A newly generated polyclonal antibody and a pan-SERCA3 antibody proved the endogenous expression of the three novel SERCA3 proteins, h3d, h3e, and r3b/c. All these data suggest that the SERCA3 gene products have a more widespread role in cellular Ca 2+ signaling than previously appreciated.

Original languageEnglish
Pages (from-to)24442-24452
Number of pages11
JournalJournal of Biological Chemistry
Volume277
Issue number27
DOIs
Publication statusPublished - Jul 5 2002

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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