Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1.
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.Here we report that timed overexpression of both the wild type (wt) and the cross-linking mutant...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3859493?pdf=render |
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| author | Yu-Fan Hsieh Guang-Yaw Liu Yi-Ju Lee Jiann-Jou Yang Katalin Sándor Zsolt Sarang Angela Bononi Paolo Pinton László Tretter Zsuzsa Szondy Gregory J Tsay |
| author_facet | Yu-Fan Hsieh Guang-Yaw Liu Yi-Ju Lee Jiann-Jou Yang Katalin Sándor Zsolt Sarang Angela Bononi Paolo Pinton László Tretter Zsuzsa Szondy Gregory J Tsay |
| author_sort | Yu-Fan Hsieh |
| collection | DOAJ |
| description | 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.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 Ca(2+) uptake. Ca(2+)-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 Ca(2+) release from the endoplasmic reticulum via both Ins3P and ryanodine sensitive receptors leading to a consequently enhanced mitochondrial Ca(2+)uptake.Our data indicate that TG2 might act as a Ca(2+) sensor to amplify endoplasmic reticulum-derived Ca(2+) signals to enhance mitochondria Ca(2+) uptake. Since enhanced mitochondrial Ca(2+) 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 Ca(2+) signals in mouse embryonic fibroblasts similar to Jurkat cells, our data might indicate a more general role of TG2 in the regulation of mitochondrial Ca(2+) homeostasis. |
| first_indexed | 2024-04-12T02:28:16Z |
| format | Article |
| id | doaj.art-c8794956117d4999ad9a1c648a9b1ddb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T02:28:16Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c8794956117d4999ad9a1c648a9b1ddb2022-12-22T03:51:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8151610.1371/journal.pone.0081516Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1.Yu-Fan HsiehGuang-Yaw LiuYi-Ju LeeJiann-Jou YangKatalin SándorZsolt SarangAngela BononiPaolo PintonLászló TretterZsuzsa SzondyGregory J TsayTransglutaminase 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.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 Ca(2+) uptake. Ca(2+)-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 Ca(2+) release from the endoplasmic reticulum via both Ins3P and ryanodine sensitive receptors leading to a consequently enhanced mitochondrial Ca(2+)uptake.Our data indicate that TG2 might act as a Ca(2+) sensor to amplify endoplasmic reticulum-derived Ca(2+) signals to enhance mitochondria Ca(2+) uptake. Since enhanced mitochondrial Ca(2+) 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 Ca(2+) signals in mouse embryonic fibroblasts similar to Jurkat cells, our data might indicate a more general role of TG2 in the regulation of mitochondrial Ca(2+) homeostasis.http://europepmc.org/articles/PMC3859493?pdf=render |
| spellingShingle | Yu-Fan Hsieh Guang-Yaw Liu Yi-Ju Lee Jiann-Jou Yang Katalin Sándor Zsolt Sarang Angela Bononi Paolo Pinton László Tretter Zsuzsa Szondy Gregory J Tsay Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1. PLoS ONE |
| title | Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1. |
| title_full | Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1. |
| title_fullStr | Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1. |
| title_full_unstemmed | Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1. |
| title_short | Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1. |
| title_sort | transglutaminase 2 contributes to apoptosis induction in jurkat t cells by modulating ca2 homeostasis via cross linking rap1gds1 |
| url | http://europepmc.org/articles/PMC3859493?pdf=render |
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