| Literature DB >> 30013108 |
Hery Urra1,2,3, Daniel R Henriquez2,4, José Cánovas1, David Villarroel-Campos2,4, Amado Carreras-Sureda1,2,3, Eduardo Pulgar1,5, Emiliano Molina4,6, Younis M Hazari1,2,3, Celia M Limia1,2,3, Sebastián Alvarez-Rojas2,4, Ricardo Figueroa1,3, Rene L Vidal1,2,7, Diego A Rodriguez3, Claudia A Rivera1,2,7, Felipe A Court2,7, Andrés Couve1,8, Ling Qi9, Eric Chevet10,11, Ryoko Akai12, Takao Iwawaki12, Miguel L Concha1,2,5, Álvaro Glavic4,6, Christian Gonzalez-Billault2,4, Claudio Hetz13,14,15,16,17.
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.Entities:
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Year: 2018 PMID： 30013108 DOI： 10.1038/s41556-018-0141-0
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824