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Title: TMBIM3/GRINA is a novel unfolded protein response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis
Authors: Rojas-Rivera, D ×
Armisén, R
Colombo, A
Martínez, G
Eguiguren, A L
Díaz, A
Kiviluoto, Santeri
Rodríguez, D
Patron, M
Rizzuto, R
Bultynck, Geert
Concha, M L
Sierralta, J
Stutzin, A
Hetz, C #
Issue Date: Jun-2012
Publisher: E. Arnold
Series Title: Cell Death and Differentiation vol:19 issue:6 pages:1013-1026
Article number: 10.1038/cdd.2011.189
Abstract: Transmembrane BAX inhibitor motif-containing (TMBIM)-6, also known as BAX-inhibitor 1 (BI-1), is an anti-apoptotic protein that belongs to a putative family of highly conserved and poorly characterized genes. Here we report the function of TMBIM3/GRINA in the control of cell death by endoplasmic reticulum (ER) stress. Tmbim3 mRNA levels are strongly upregulated in cellular and animal models of ER stress, controlled by the PERK signaling branch of the unfolded protein response. TMBIM3/GRINA synergies with TMBIM6/BI-1 in the modulation of ER calcium homeostasis and apoptosis, associated with physical interactions with inositol trisphosphate receptors. Loss-of-function studies in D. melanogaster demonstrated that TMBIM3/GRINA and TMBIM6/BI-1 have synergistic activities against ER stress in vivo. Similarly, manipulation of TMBIM3/GRINA levels in zebrafish embryos revealed an essential role in the control of apoptosis during neuronal development and in experimental models of ER stress. These findings suggest the existence of a conserved group of functionally related cell death regulators across species beyond the BCL-2 family of proteins operating at the ER membrane.Cell Death and Differentiation advance online publication, 13 January 2012; doi:10.1038/cdd.2011.189.
ISSN: 1350-9047
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular and Cellular Signaling
× corresponding author
# (joint) last author

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