Cleavage of the plasma membrane Ca2+ ATPase during apoptosis

Katalin Pászty, Géza Antalffy, Luca Hegedüs, Rita Padányi, Alan R. Penheiter, Adelaida G. Filoteo, John T. Penniston, Ágnes Enyedi

Research output: Conference contribution

15 Citations (Scopus)

Abstract

Maintenance of Ca2+ homeostasis is essential for normal cellular function and survival. Recent evidences suggest that Ca2+ is also an important player of apoptosis. We demonstrated that the plasma membrane Ca 2+ ATPase (PMCA) isoform 4b, a key element of cellular Ca 2+ homeostasis, was cleaved by caspase-3 during the course of apoptosis. This cleavage of PMCA removed the entire regulatory region from the C terminus, leaving behind a 120-kDa catalytic fragment. Since loss of PMCA activity could lead to intracellular Ca2+ overload and consequently necrotic cell death, an important question is whether the apoptotic fragment of PMCA retains full activity or it is inactivated. To address this question, we constructed a C-terminally truncated mutant that corresponded to the caspase-3 fragment of PMCA4b and showed that it was fully and constitutively active. Thismutant was targeted properly to the plasma membrane when it was expressed stably or transiently in several different cell lines. We followed truncation of PMCA during apoptosis induced by mitochondrial or receptor-mediated pathways and found that a similar fragment of 120 kDa was formed and remained intact for several hours after treatment. We have also demonstrated that the caspase-3 cleavage site is an important structural element of PMCA and found that the accessibility of the caspase-3 site depended strongly on the conformational state of the protein.

Original languageEnglish
Title of host publicationSodium-Calcium Exchange and the Plasma Membrane Ca2+ATPase in Ce;; Funcyion
Subtitle of host publicationFifth International Conference
PublisherBlackwell Publishing Inc.
Pages440-450
Number of pages11
ISBN (Print)1573316490, 9781573316491
DOIs
Publication statusPublished - márc. 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1099
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Pászty, K., Antalffy, G., Hegedüs, L., Padányi, R., Penheiter, A. R., Filoteo, A. G., Penniston, J. T., & Enyedi, Á. (2007). Cleavage of the plasma membrane Ca2+ ATPase during apoptosis. In Sodium-Calcium Exchange and the Plasma Membrane Ca2+ATPase in Ce;; Funcyion: Fifth International Conference (pp. 440-450). (Annals of the New York Academy of Sciences; Vol. 1099). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1387.003