Requirement of biphasic calcium release from the endoplasmic reticulum for Fas-mediated apoptosis

Ann L. Wozniak, Xinmin Wang, Emily S. Stieren, Shelby G. Scarbrough, Cornelis Elferink, Darren Boehning

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Fas receptor is a member of the tumor necrosis factor-α family of death receptors that mediate physiologic apoptotic signaling. To investigate the molecular mechanisms regulating calcium mobilization during Fas-mediated apoptosis, we have analyzed the sequential steps leading to altered calcium homeostasis and cell death in response to activation of the Fas receptor. We show that Fas-mediated apoptosis requires endoplasmic reticulum-mediated calcium release in a mechanism dependent on phospholipase C-γ1 (PLC-γ1) activation and Ca2+ release from inositol 1,4,5-trisphosphate receptor (IP3R) channels. The kinetics of Ca2+ release were biphasic, demonstrating a rapid elevation caused by PLC-γ1 activation and a delayed and sustained increase caused by cytochrome c binding to IP 3R. Blocking either phase of Ca2+ mobilization was cytoprotective, highlighting PLC-γ1 and IP3R as possible therapeutic targets for disorders associated with Fas signaling.

Original languageEnglish (US)
Pages (from-to)709-714
Number of pages6
JournalJournal of Cell Biology
Volume175
Issue number5
DOIs
StatePublished - Dec 2006

Fingerprint

Type C Phospholipases
Endoplasmic Reticulum
CD95 Antigens
Apoptosis
Calcium
Inositol 1,4,5-Trisphosphate Receptors
Death Domain Receptors
Cytochromes c
Homeostasis
Cell Death
Tumor Necrosis Factor-alpha
Therapeutics

ASJC Scopus subject areas

  • Cell Biology

Cite this

Requirement of biphasic calcium release from the endoplasmic reticulum for Fas-mediated apoptosis. / Wozniak, Ann L.; Wang, Xinmin; Stieren, Emily S.; Scarbrough, Shelby G.; Elferink, Cornelis; Boehning, Darren.

In: Journal of Cell Biology, Vol. 175, No. 5, 12.2006, p. 709-714.

Research output: Contribution to journalArticle

Wozniak, Ann L. ; Wang, Xinmin ; Stieren, Emily S. ; Scarbrough, Shelby G. ; Elferink, Cornelis ; Boehning, Darren. / Requirement of biphasic calcium release from the endoplasmic reticulum for Fas-mediated apoptosis. In: Journal of Cell Biology. 2006 ; Vol. 175, No. 5. pp. 709-714.
@article{420664f5bb234df1a41ca4735ed85ad4,
title = "Requirement of biphasic calcium release from the endoplasmic reticulum for Fas-mediated apoptosis",
abstract = "Fas receptor is a member of the tumor necrosis factor-α family of death receptors that mediate physiologic apoptotic signaling. To investigate the molecular mechanisms regulating calcium mobilization during Fas-mediated apoptosis, we have analyzed the sequential steps leading to altered calcium homeostasis and cell death in response to activation of the Fas receptor. We show that Fas-mediated apoptosis requires endoplasmic reticulum-mediated calcium release in a mechanism dependent on phospholipase C-γ1 (PLC-γ1) activation and Ca2+ release from inositol 1,4,5-trisphosphate receptor (IP3R) channels. The kinetics of Ca2+ release were biphasic, demonstrating a rapid elevation caused by PLC-γ1 activation and a delayed and sustained increase caused by cytochrome c binding to IP 3R. Blocking either phase of Ca2+ mobilization was cytoprotective, highlighting PLC-γ1 and IP3R as possible therapeutic targets for disorders associated with Fas signaling.",
author = "Wozniak, {Ann L.} and Xinmin Wang and Stieren, {Emily S.} and Scarbrough, {Shelby G.} and Cornelis Elferink and Darren Boehning",
year = "2006",
month = "12",
doi = "10.1083/jcb.200608035",
language = "English (US)",
volume = "175",
pages = "709--714",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "5",

}

TY - JOUR

T1 - Requirement of biphasic calcium release from the endoplasmic reticulum for Fas-mediated apoptosis

AU - Wozniak, Ann L.

AU - Wang, Xinmin

AU - Stieren, Emily S.

AU - Scarbrough, Shelby G.

AU - Elferink, Cornelis

AU - Boehning, Darren

PY - 2006/12

Y1 - 2006/12

N2 - Fas receptor is a member of the tumor necrosis factor-α family of death receptors that mediate physiologic apoptotic signaling. To investigate the molecular mechanisms regulating calcium mobilization during Fas-mediated apoptosis, we have analyzed the sequential steps leading to altered calcium homeostasis and cell death in response to activation of the Fas receptor. We show that Fas-mediated apoptosis requires endoplasmic reticulum-mediated calcium release in a mechanism dependent on phospholipase C-γ1 (PLC-γ1) activation and Ca2+ release from inositol 1,4,5-trisphosphate receptor (IP3R) channels. The kinetics of Ca2+ release were biphasic, demonstrating a rapid elevation caused by PLC-γ1 activation and a delayed and sustained increase caused by cytochrome c binding to IP 3R. Blocking either phase of Ca2+ mobilization was cytoprotective, highlighting PLC-γ1 and IP3R as possible therapeutic targets for disorders associated with Fas signaling.

AB - Fas receptor is a member of the tumor necrosis factor-α family of death receptors that mediate physiologic apoptotic signaling. To investigate the molecular mechanisms regulating calcium mobilization during Fas-mediated apoptosis, we have analyzed the sequential steps leading to altered calcium homeostasis and cell death in response to activation of the Fas receptor. We show that Fas-mediated apoptosis requires endoplasmic reticulum-mediated calcium release in a mechanism dependent on phospholipase C-γ1 (PLC-γ1) activation and Ca2+ release from inositol 1,4,5-trisphosphate receptor (IP3R) channels. The kinetics of Ca2+ release were biphasic, demonstrating a rapid elevation caused by PLC-γ1 activation and a delayed and sustained increase caused by cytochrome c binding to IP 3R. Blocking either phase of Ca2+ mobilization was cytoprotective, highlighting PLC-γ1 and IP3R as possible therapeutic targets for disorders associated with Fas signaling.

UR - http://www.scopus.com/inward/record.url?scp=33845288349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845288349&partnerID=8YFLogxK

U2 - 10.1083/jcb.200608035

DO - 10.1083/jcb.200608035

M3 - Article

C2 - 17130290

AN - SCOPUS:33845288349

VL - 175

SP - 709

EP - 714

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 5

ER -