| TMBIM3/GRINA is a novel unfolded protein response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis. | |
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MedLine Citation:
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PMID: 22240901 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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D Rojas-Rivera; R Armisén; A Colombo; G Martínez; A L Eguiguren; A Díaz; S Kiviluoto; D Rodríguez; M Patron; R Rizzuto; G Bultynck; M L Concha; J Sierralta; A Stutzin; C Hetz |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-13 |
Journal Detail:
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Title: Cell death and differentiation Volume: - ISSN: 1476-5403 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile [2] Center for Molecular Studies of the Cell, Faculty of Medicine, University of Chile, Santiago, Chile [3] Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile. |
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