Cleavage of the plasma membrane Ca2+ ATPase during apoptosis

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

Research output: Chapter in Book/Report/Conference proceedingConference 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 publicationAnnals of the New York Academy of Sciences
Pages440-450
Number of pages11
Volume1099
DOIs
Publication statusPublished - Mar 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1099
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Calcium-Transporting ATPases
Cell membranes
Adenosine Triphosphatases
Cell Membrane
Apoptosis
Caspase 3
Homeostasis
Nucleic Acid Regulatory Sequences
Cell death
Protein Isoforms
Cell Death
Cells
Maintenance
Cell Line

Keywords

  • Activation
  • Apoptosis
  • Calmodulin
  • Caspase-3
  • Localization
  • Plasma membrane Ca ATPase
  • Structure function
  • Truncatedmutant

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pászty, K., Antalffy, G., Hegedüs, L., Padányi, R., Penheiter, A. R., Filoteo, A. G., ... Enyedi, A. (2007). Cleavage of the plasma membrane Ca2+ ATPase during apoptosis. In Annals of the New York Academy of Sciences (Vol. 1099, pp. 440-450). (Annals of the New York Academy of Sciences; Vol. 1099). https://doi.org/10.1196/annals.1387.003

Cleavage of the plasma membrane Ca2+ ATPase during apoptosis. / Pászty, K.; Antalffy, Géza; Hegedüs, Luca; Padányi, Rita; Penheiter, Alan R.; Filoteo, Adelaida G.; Penniston, John T.; Enyedi, A.

Annals of the New York Academy of Sciences. Vol. 1099 2007. p. 440-450 (Annals of the New York Academy of Sciences; Vol. 1099).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Pászty, K, Antalffy, G, Hegedüs, L, Padányi, R, Penheiter, AR, Filoteo, AG, Penniston, JT & Enyedi, A 2007, Cleavage of the plasma membrane Ca2+ ATPase during apoptosis. in Annals of the New York Academy of Sciences. vol. 1099, Annals of the New York Academy of Sciences, vol. 1099, pp. 440-450. https://doi.org/10.1196/annals.1387.003
Pászty K, Antalffy G, Hegedüs L, Padányi R, Penheiter AR, Filoteo AG et al. Cleavage of the plasma membrane Ca2+ ATPase during apoptosis. In Annals of the New York Academy of Sciences. Vol. 1099. 2007. p. 440-450. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1387.003
Pászty, K. ; Antalffy, Géza ; Hegedüs, Luca ; Padányi, Rita ; Penheiter, Alan R. ; Filoteo, Adelaida G. ; Penniston, John T. ; Enyedi, A. / Cleavage of the plasma membrane Ca2+ ATPase during apoptosis. Annals of the New York Academy of Sciences. Vol. 1099 2007. pp. 440-450 (Annals of the New York Academy of Sciences).
@inproceedings{6509cfeeddf549c98bb20b9467e65fc1,
title = "Cleavage of the plasma membrane Ca2+ ATPase during apoptosis",
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.",
keywords = "Activation, Apoptosis, Calmodulin, Caspase-3, Localization, Plasma membrane Ca ATPase, Structure function, Truncatedmutant",
author = "K. P{\'a}szty and G{\'e}za Antalffy and Luca Heged{\"u}s and Rita Pad{\'a}nyi and Penheiter, {Alan R.} and Filoteo, {Adelaida G.} and Penniston, {John T.} and A. Enyedi",
year = "2007",
month = "3",
doi = "10.1196/annals.1387.003",
language = "English",
isbn = "1573316490",
volume = "1099",
series = "Annals of the New York Academy of Sciences",
pages = "440--450",
booktitle = "Annals of the New York Academy of Sciences",

}

TY - GEN

T1 - Cleavage of the plasma membrane Ca2+ ATPase during apoptosis

AU - Pászty, K.

AU - Antalffy, Géza

AU - Hegedüs, Luca

AU - Padányi, Rita

AU - Penheiter, Alan R.

AU - Filoteo, Adelaida G.

AU - Penniston, John T.

AU - Enyedi, A.

PY - 2007/3

Y1 - 2007/3

N2 - 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.

AB - 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.

KW - Activation

KW - Apoptosis

KW - Calmodulin

KW - Caspase-3

KW - Localization

KW - Plasma membrane Ca ATPase

KW - Structure function

KW - Truncatedmutant

UR - http://www.scopus.com/inward/record.url?scp=34248584963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248584963&partnerID=8YFLogxK

U2 - 10.1196/annals.1387.003

DO - 10.1196/annals.1387.003

M3 - Conference contribution

C2 - 17446484

AN - SCOPUS:34248584963

SN - 1573316490

SN - 9781573316491

VL - 1099

T3 - Annals of the New York Academy of Sciences

SP - 440

EP - 450

BT - Annals of the New York Academy of Sciences

ER -