| First Author | Urra H | Year | 2018 |
| Journal | Nat Cell Biol | Volume | 20 |
| Issue | 8 | Pages | 942-953 |
| PubMed ID | 30013108 | Mgi Jnum | J:269148 |
| Mgi Id | MGI:6271426 | Doi | 10.1038/s41556-018-0141-0 |
| Citation | Urra H, et al. (2018) IRE1alpha governs cytoskeleton remodelling and cell migration through a direct interaction with filamin A. Nat Cell Biol 20(8):942-953 |
| abstractText | 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 IRE1alpha. Filamin A is an actin crosslinking factor involved in cytoskeleton remodelling. We show that IRE1alpha controls actin cytoskeleton dynamics and affects cell migration upstream of filamin A. The regulation of cytoskeleton dynamics by IRE1alpha is independent of its canonical role as a UPR mediator, serving instead as a scaffold that recruits and regulates filamin A. Targeting IRE1alpha expression in mice affected normal brain development, generating a phenotype resembling periventricular heterotopia, a disease linked to the loss of function of filamin A. IRE1alpha also modulated cell movement and cytoskeleton dynamics in fly and zebrafish models. This study unveils an unanticipated biological function of IRE1alpha in cell migration, whereby filamin A operates as an interphase between the UPR and the actin cytoskeleton. |
