Transglutaminase 2 contributes to apoptosis induction in jurkat t cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1

Yu Fan Hsieh, Guang Yaw Liu, Yi Ju Lee, Jiann Jou Yang, Katalin Sándor, Z. Sarang, Angela Bononi, Paolo Pinton, L. Tretter, Z. Szondy, Gregory J. Tsay

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Transglutaminase 2 (TG2) is a protein cross-linking enzyme known to be associated with the in vivo apoptosis program of T cells. However, its role in the T cell apoptosis program was not investigated yet. Results: Here we report that timed overexpression of both the wild type (wt) and the cross-linking mutant of TG2 induced apoptosis in Jurkat T cells, the wt being more effective. Part of TG2 colocalised with mitochondria. WtTG2-induced apoptosis was characterized by enhanced mitochondrial Ca2+ uptake. Ca2+-activated wtTG2 cross-linked RAP1, GTP-GDP dissociation stimulator 1, an unusual guanine exchange factor acting on various small GTPases, to induce a yet uncharacterized signaling pathway that was able to promote the Ca2+ release from the endoplasmic reticulum via both Ins3P and ryanodine sensitive receptors leading to a consequently enhanced mitochondrial Ca2+uptake. Conclusions: Our data indicate that TG2 might act as a Ca2+ sensor to amplify endoplasmic reticulum-derived Ca2+ signals to enhance mitochondria Ca2+ uptake. Since enhanced mitochondrial Ca2+ levels were previously shown to sensitize mitochondria for various apoptotic signals, our data demonstrate a novel mechanism through which TG2 can contribute to the induction of apoptosis in certain cell types. Since, as compared to knock out cells, physiological levels of TG2 affected Ca2+ signals in mouse embryonic fibroblasts similar to Jurkat cells, our data might indicate a more general role of TG2 in the regulation of mitochondrial Ca2+ homeostasis.

Original languageEnglish
Article numbere81516
JournalPLoS One
Volume8
Issue number12
DOIs
Publication statusPublished - Dec 11 2013

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Jurkat Cells
protein-glutamine gamma-glutamyltransferase
crosslinking
homeostasis
Homeostasis
apoptosis
Apoptosis
calcium
Mitochondria
T-cells
cells
T-Lymphocytes
Endoplasmic Reticulum
mitochondria
T-lymphocytes
uptake mechanisms
endoplasmic reticulum
Guanine Nucleotide Exchange Factors
Ryanodine
Ryanodine Receptor Calcium Release Channel

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Transglutaminase 2 contributes to apoptosis induction in jurkat t cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1. / Hsieh, Yu Fan; Liu, Guang Yaw; Lee, Yi Ju; Yang, Jiann Jou; Sándor, Katalin; Sarang, Z.; Bononi, Angela; Pinton, Paolo; Tretter, L.; Szondy, Z.; Tsay, Gregory J.

In: PLoS One, Vol. 8, No. 12, e81516, 11.12.2013.

Research output: Contribution to journalArticle

Hsieh, Yu Fan ; Liu, Guang Yaw ; Lee, Yi Ju ; Yang, Jiann Jou ; Sándor, Katalin ; Sarang, Z. ; Bononi, Angela ; Pinton, Paolo ; Tretter, L. ; Szondy, Z. ; Tsay, Gregory J. / Transglutaminase 2 contributes to apoptosis induction in jurkat t cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1. In: PLoS One. 2013 ; Vol. 8, No. 12.
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AU - Sándor, Katalin

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AU - Bononi, Angela

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