IRE1α governs cytoskeleton remodelling and cell migration through a direct interaction with filamin A

Autor: Ricardo Figueroa, Daniel R. Henríquez, Diego A. Rodriguez, Andrés Couve, Sebastián Alvarez-Rojas, Felipe A. Court, Takao Iwawaki, Alvaro Glavic, David Villarroel-Campos, José Cánovas, Amado Carreras-Sureda, Eduardo Pulgar, Rene L. Vidal, Miguel L. Concha, Ryoko Akai, Claudio Hetz, Hery Urra, Eric Chevet, Celia M Limia, Younis Hazari, Ling Qi, Claudia A Rivera, Christian Gonzalez-Billault, Emiliano Molina
Přispěvatelé: Universidad de Santiago de Chile [Santiago] (USACH), Universidad Mayor, University of Michigan [Ann Arbor], University of Michigan System, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), FONDECYT [3160461, 1140549, 1180993, 1140325, 1150608, 1150766, 3160478, 3150113, 1140522], Millennium Institute [P09-015-F], FONDAP [15150012, 15090007], ECOS-CONICYT [170032], PIA-CONICYT [ACT1401], NIH [R01 Gm113188], CONICYT [ACT1402], European Commission RD MSCA-RISE [734749], Michael J Fox Foundation for Parkinson's Research-Target Validation grant [9277], FONDEF [ID16I10223, D11E1007], US Office of Naval Research-Global (ONR-G) [N62909-16-1-2003], US Air Force Office of Scientific Research [FA9550-16-1-0384], ALSRP Therapeutic Idea Award [AL150111], Muscular Dystrophy Association [382453], CONICYT-Brazil [441921/2016-7], Toray Science Foundation, CONICYT fellowship [21160967], CONICYT research grant, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
animal structures
Filamins
[SDV.CAN]Life Sciences [q-bio]/Cancer
macromolecular substances
Protein Serine-Threonine Kinases
Filamin
Evolution
Molecular
03 medical and health sciences
Mice
0302 clinical medicine
Periventricular Nodular Heterotopia
Cell Movement
Endoribonucleases
Animals
Drosophila Proteins
Humans
Protein Interaction Domains and Motifs
Phosphorylation
Cytoskeleton
Actin
Zebrafish
Mice
Knockout
Neurons
Chemistry
Endoplasmic reticulum
Cell migration
Cell Biology
Fibroblasts
Zebrafish Proteins
Actin cytoskeleton
Cell biology
body regions
Actin Cytoskeleton
Kinetics
030104 developmental biology
Proteostasis
Drosophila melanogaster
HEK293 Cells
biological sciences
Unfolded protein response
Unfolded Protein Response
Female
030217 neurology & neurosurgery
Protein Binding
Signal Transduction
Zdroj: Nature Cell Biology
Nature Cell Biology, Nature Publishing Group, 2018, 20 (8), pp.942-953. ⟨10.1038/s41556-018-0141-0⟩
Artículos CONICYT
CONICYT Chile
instacron:CONICYT
Nature Cell Biology, 2018, 20 (8), pp.942-953. ⟨10.1038/s41556-018-0141-0⟩
ISSN: 1476-4679
1465-7392
DOI: 10.1038/s41556-018-0141-0⟩
Popis: International audience; 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 IRE1 alpha. Filamin A is an actin crosslinking factor involved in cytoskeleton remodelling. We show that IRE1 alpha controls actin cytoskeleton dynamics and affects cell migration upstream of filamin A. The regulation of cytoskeleton dynamics by IRE1 alpha is independent of its canonical role as a UPR mediator, serving instead as a scaffold that recruits and regulates filamin A. Targeting IRE1 alpha expression in mice affected normal brain development, generating a phenotype resembling periventricular heterotopia, a disease linked to the loss of function of filamin A. IRE1 alpha also modulated cell movement and cytoskeleton dynamics in fly and zebrafish models. This study unveils an unanticipated biological function of IRE1 alpha in cell migration, whereby filamin A operates as an interphase between the UPR and the actin cytoskeleton.
Databáze: OpenAIRE
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