TMBIM3/GRINA is a novel unfolded protein response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis

Rojas-Rivera, D; Armisen, R; Colombo, A; Martinez, G; Eguiguren, A. L.; Diaz A.; Kiviluoto S; Rodriguez D.; Patron, M; Rizzuto, R; Bultynck G.; Concha, M. L.; Sierralta, J; Stutzin A.; hetz C.

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. © 2012 Macmillan Publishers Limited. All rights reserved.

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Título según WOS: TMBIM3/GRINA is a novel unfolded protein response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis
Título según SCOPUS: TMBIM3/GRINA is a novel unfolded protein response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis
Título de la Revista: CELL DEATH AND DIFFERENTIATION
Volumen: 19
Número: 6
Editorial: Nature Publishing Group
Fecha de publicación: 2012
Página de inicio: 1013
Página final: 1026
Idioma: English
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-84860774401&partnerID=40&md5=ac1c612f8de77aaac4a8f7677604ad43
DOI:

10.1038/cdd.2011.189

Notas: ISI, SCOPUS