ZFIN ID: ZDB-PUB-180718-4
IRE1α governs cytoskeleton remodelling and cell migration through a direct interaction with filamin A
Urra, H., Henriquez, D.R., Cánovas, J., Villarroel-Campos, D., Carreras-Sureda, A., Pulgar, E., Molina, E., Hazari, Y.M., Limia, C.M., Alvarez-Rojas, S., Figueroa, R., Vidal, R.L., Rodriguez, D.A., Rivera, C.A., Court, F.A., Couve, A., Qi, L., Chevet, E., Akai, R., Iwawaki, T., Concha, M.L., Glavic, Á., Gonzalez-Billault, C., Hetz, C.
Date: 2018
Source: Nature cell biology   20(8): 942-953 (Journal)
Registered Authors: Concha, Miguel
Keywords: none
MeSH Terms:
  • Actin Cytoskeleton/metabolism*
  • Animals
  • Cell Movement*
  • Drosophila Proteins/genetics
  • Drosophila Proteins/metabolism
  • Drosophila melanogaster/genetics
  • Drosophila melanogaster/metabolism
  • Endoribonucleases/deficiency
  • Endoribonucleases/genetics
  • Endoribonucleases/metabolism*
  • Evolution, Molecular
  • Female
  • Fibroblasts/metabolism*
  • Filamins/genetics
  • Filamins/metabolism*
  • HEK293 Cells
  • Humans
  • Kinetics
  • Male
  • Mice
  • Mice, Knockout
  • Neurons/metabolism*
  • 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
  • Protein-Serine-Threonine Kinases/metabolism*
  • Signal Transduction
  • Unfolded Protein Response
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 30013108 Full text @ Nat. Cell Biol.
ABSTRACT
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.
ADDITIONAL INFORMATION