Fantastic work by Inspired partner Claudio Hetz and co-author Eric Chevet showing an unanticipated role for IRE1α in cell migration.
In this study they showed that IRE1α controls actin cytoskeleton dynamics and affects cell migration upstream of filamin A. Their demonstrated that IRE1 interacts with Filamin A which is an actin crosslinking factor involved in cytoskeleton remodelling. IRE1 regulates cytoskeleton dynamics 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.
Their work unveils an unanticipated biological function of IRE1α in cell migration, whereby filamin A operates as an interphase between the UPR and the actin cytoskeleton. See doi.org/10.1038/s41556-018-0141-0