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Tytuł:
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IRE1α governs cytoskeleton remodelling and cell migration through a direct interaction with filamin A.
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Autorzy:
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Urra H; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Henriquez DR; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile.
Cánovas J; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.
Villarroel-Campos D; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile.
Carreras-Sureda A; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Pulgar E; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Program of Anatomy and Developmental Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Molina E; Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile.; Center for Genome Regulation, Faculty of Sciences, University of Chile, Santiago, Chile.
Hazari YM; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Limia CM; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Alvarez-Rojas S; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile.
Figueroa R; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Vidal RL; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.
Rodriguez DA; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Rivera CA; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.
Court FA; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.
Couve A; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Department of Neuroscience, Faculty of Medicine, University of Chile, Santiago, Chile.
Qi L; Department of Molecular and Integrative Physiology, Division of Metabolism, Endocrinology and Diabetes, The University of Michigan Medical School, Ann Arbor, MI, USA.
Chevet E; INSERM U1242 Chemistry, Oncogenesis, Stress and Signaling, University of Rennes 1, Rennes, France.; Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France.
Akai R; Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Uchinada, Japan.
Iwawaki T; Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Uchinada, Japan.
Concha ML; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Program of Anatomy and Developmental Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Glavic Á; Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile.; Center for Genome Regulation, Faculty of Sciences, University of Chile, Santiago, Chile.
Gonzalez-Billault C; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile.; Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile.
Hetz C; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile. .; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile. .; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile. .; The Buck Institute for Research in Aging, Novato, CA, USA. .; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA. .
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Źródło:
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Nature cell biology [Nat Cell Biol] 2018 Aug; Vol. 20 (8), pp. 942-953. Date of Electronic Publication: 2018 Jul 16.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't; Video-Audio Media
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Język:
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English
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Imprint Name(s):
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Original Publication: London : Macmillan Magazines Ltd., [1999-
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MeSH Terms:
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Cell Movement*
Actin Cytoskeleton/*metabolism
Endoribonucleases/*metabolism
Fibroblasts/*metabolism
Filamins/*metabolism
Neurons/*metabolism
Protein Serine-Threonine Kinases/*metabolism
Animals ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Endoribonucleases/deficiency ; Endoribonucleases/genetics ; Evolution, Molecular ; Female ; Filamins/genetics ; HEK293 Cells ; Humans ; Kinetics ; Male ; Mice ; Mice, Knockout ; Neurons/pathology ; Periventricular Nodular Heterotopia/genetics ; Periventricular Nodular Heterotopia/metabolism ; Periventricular Nodular Heterotopia/pathology ; Phosphorylation ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Serine-Threonine Kinases/deficiency ; Protein Serine-Threonine Kinases/genetics ; Signal Transduction ; Unfolded Protein Response ; Zebrafish/genetics ; Zebrafish/metabolism ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism
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Grant Information:
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R01 GM113188 United States GM NIGMS NIH HHS
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Substance Nomenclature:
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0 (Drosophila Proteins)
0 (FLNA protein, human)
0 (Filamins)
0 (FlnA protein, mouse)
0 (Zebrafish Proteins)
EC 2.7.11.1 (ERN1 protein, human)
EC 2.7.11.1 (Ern1 protein, mouse)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 3.1.- (Endoribonucleases)
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Entry Date(s):
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Date Created: 20180718 Date Completed: 20190415 Latest Revision: 20211204
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Update Code:
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20240105
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DOI:
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10.1038/s41556-018-0141-0
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PMID:
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30013108
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Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a signalling network known as the unfolded protein response (UPR). Here, we identified filamin A as a major binding partner of the ER stress transducer IRE1α. Filamin A is an actin crosslinking factor involved in cytoskeleton remodelling. We show that IRE1α controls actin cytoskeleton dynamics and affects cell migration upstream of filamin A. The regulation of cytoskeleton dynamics by IRE1α is independent of its canonical role as a UPR mediator, serving instead as a scaffold that recruits and regulates filamin A. Targeting IRE1α expression in mice affected normal brain development, generating a phenotype resembling periventricular heterotopia, a disease linked to the loss of function of filamin A. IRE1α also modulated cell movement and cytoskeleton dynamics in fly and zebrafish models. This study unveils an unanticipated biological function of IRE1α in cell migration, whereby filamin A operates as an interphase between the UPR and the actin cytoskeleton.
Erratum in: Nat Cell Biol. 2018 Oct;20(10):1228. (PMID: 30089843)
Erratum in: Nat Cell Biol. 2021 May;23(5):577. (PMID: 33907311)
