Complexes of ?6?4 integrin and vimentin act as signaling hubs to regulate epithelial cell migration.

ABSTRACT: We find that clusters of ?4 integrin, organized into distinct puncta, localize along vimentin filaments within lamellipodia at the cell edge of A549 cells, as assessed by interferometric photoactivated localization microscopy. Moreover, puncta and vimentin filaments exhibit a dynamic interplay in live cells, as viewed by structured-illumination microscopy, with ?4 integrin puncta that associate with vimentin persisting for longer than those that do not. Interestingly, in A549 cells ?4 integrin regulates vimentin cytoskeleton organization. When ?4 integrin is knocked down there is a loss of vimentin filaments from lamellipodia. However, in these conditions, vimentin filaments instead concentrate around the nucleus. Although ?4 integrin organization is unaffected in vimentin-deficient A549 cells, such cells move in a less-directed fashion and exhibit reduced Rac1 activity, mimicking the phenotype of ?4 integrin-deficient A549 cells. Moreover, in vimentin-deficient cells, Rac1 fails to cluster at sites enriched in ?6?4 integrin heterodimers. The aberrant motility of both ?4 integrin and vimentin-deficient cells is rescued by expression of active Rac1, leading us to propose that complexes of ?4 integrin and vimentin act as signaling hubs, regulating cell motility behavior.

SUBMITTER: Colburn ZT 

PROVIDER: S-EPMC6080603 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature