| First Author | Hsieh YF | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 12 | Pages | e81516 |
| PubMed ID | 24349085 | Mgi Jnum | J:211321 |
| Mgi Id | MGI:5574435 | Doi | 10.1371/journal.pone.0081516 |
| Citation | Hsieh YF, et al. (2013) Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1. PLoS One 8(12):e81516 |
| abstractText | 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 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. CONCLUSIONS: 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. |
